As with any addiction, there are both short and long-term effects that play a crucial role in shaping the way the physical and mental behaviors of an individual can change with increased alcohol intake. As human beings are not all the same due to the differences in physical appearance and gender, responses differ with alcohol. Blood alcohol concentration (BAC) is used to determine the effects of alcohol (1). Alcohol addiction has underlying short-term and long-term effects on an individual’s health and well being depending on the amount of alcohol used in a given period of time. Constant abuse of alcohol will eventually result in long-term effects and relatively small and dispersed uses of alcohol will result in short-term effects after five minutes (1). Both types of effects are associated with reduced cognitive function. Some examples of short-term effects are dizziness, slurred speech, vomiting, and impairment of judgment and coordination (1). Long-term effects of alcohol dependence include heart damage, liver disease, brain damage and digestive system disorders (1). Both types of effects have an endless list of symptoms. Extensive research has been done to correlate the different types of alcohol abuse, addiction and dependence with their diverse effects. Thus far, research has identified some effects such as, neurodegeneration (inhibition of neural stem cell proliferation) (2), late onset of Alzheimer’s disease (deficiency of ALDH2 gene (for breakdown of acetylaldehyde) which increases risk of LOAD) (3) and other deleterious effects that occur due to long-term alcohol abuse. Each has specific genes of the brain that are affected and different detrimental neuronal effects.















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SHORT TERM EFFECTS


Alcohol is scientifically known to be a neurochemical inhibitor that induces an effect towards its consumers (4). These effects are separated into two types, short and long-term effects. Short-term effects succumb due to binge drinking (consumption of four or more alcoholic beverages during a single period of time for both genders) (4). Long-term effects, on the other hand, are caused by heavy drinking, which is defined as the consumption of two or more alcoholic beverages per day for both genders (4).

Studies conducted by researchers at the University of Sussex on binge drinking found that there was a greater behavioral relationship between binge drinking and eating (5). These findings associated alcohol intake with appetite and obesity due to the studies that had proven that short-term consumption of alcohol proportionally increased the energy intake within food consumption (5). This is one of many short-term affects affiliated with binge drinking. As mentioned above in the introduction, there are many different types of effects that occur due to alcohol consumption ranging from minor to major issues. The outcomes of these effects are based on blood alcohol concentration (BAC) because all humans have different body types, which respond differently to alcohol. One of the most affected parts of the human body after the consumption of alcohol is the prefrontal cortex (PFC).

The PFC’s major function is to collect and perceive inputs from cortical and sub-cortical regions of the brain and to provide responses towards these inputs in order to be executed. Some examples of these responses include executive plans to obtain rewards (cognitive) and prevent harm to the individual executing these actions (behavioral) (6). When alcohol is consumed, it affects the mesolimbic dopamine (DA) system of the brain through its regulation of dopamine release . This system is associated with the ventral tegmental area (VTA) and projects to structures such as the nucleus accumbens (NAc), amygdala, and hippocampus (6). Evidences have shown that changes to the PFC due to short-term alcohol consumption are negatively associated later with alcohol addiction (6). Studies on acute ethanol consumption in humans have concluded that alcohol causes short-term negative effects in the PFC towards executive functions in tasks such as, spatial recognition, planning, decision-making in gambling and the distortion of senses (6).


One of the most commonly experienced short-term effects of binge drinking is a phenomenon called an alcoholic blackout. An alcoholic blackout is defined as the loss of memory towards previous actions committed and events during a period of acute alcohol consumption while in a state of consciousness (7). There are two types of blackouts, complete (en-bloc) or partial (fragmentary, or grayout). A complete blackout is characterized by complete and permanent memory loss and a partial blackout is characterized by partial memory loss that can be recalled with helpful clues and reminders (7). Blackouts occur to binge drinkers who consume alcohol too rapidly or in excess of their limit, both contribute to an increase in an individuals BAC. Studies done in the past report that age, gender and socioeconomic factors determine the amounts of alcohol consumed and that the majority of younger generations experience blackouts more frequently than subsequent generations (7). As blackouts are known to cause a dysfunction in memory formation, alcohol specifically targets the encoding state in the memory formation pathway for episodic memory (includes the time, place, and other information about the occurrence of the event) (7). Memory formation is associated with long-term potentiation (LTP) and studies have proven that alcohol inhibits LTP by preventing the proper functioning of the N-methyl-D-aspartate (NMDA) receptor. The NMDA receptor is needed for initiating LTP in area CA1 of the hippocampus. Alcohol prevents this by inhibiting the NMDA receptor and spreading of the γ-aminobutyric acid A (GABAA) receptor, preventing the activation of the NMDA receptor and ultimately ceasing LTP (7).
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Figure 2. Schematic brain overview of VTA pathway
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Figure 3. Different types of alcohol addiction and results


Short-term effects are known to have a stronger effect on cognitive decline compared to long-term effects. Other types of common short-term effects experienced by binge drinkers include diarrhea, headaches, comas and difficulty breathing (7). In order to avoid these effects and health complications in the future, one must learn to control their own alcohol intake and take necessary precautions to keep a healthy life.




HIPPOCAMPAL NEURODEGENERATION



One of the many long-term effects of alcohol addiction is an increase in hippocampal neurodegeneration. Richardson et al. have noted that chronic alcohol consumption is associated with deficits in structure and function of the hippocampus (8). In rodent models, under different conditions of alcohol exposure, researchers were able to conclude that alcohol addiction reduced cell growth and survival in the medial prefrontal cortex (mPFC).

There was also a reduction in the proliferation, differentiation and neurogenesis in the hippocampus, which also resulted in apoptosis (programmed cell death) and neuronal degeneration due to alcohol exposure (8). These findings support that alcohol does have a major negative effect on the hippocampus and on the creation of new cell and their growth in the brain. Furthermore, these effects can result in many complications such as nerve damage and later onset of Alzheimer’s disease.
Bromo-deoxyuridine (BrdU) is a marker of proliferating cells that is injected during DNA synthesis in order to visualize cell survival and differentiation during abstinence from alcohol (9). Studies done by Morris et al. on rat models injected with BrdU showed that after 4 days of binge drinking resulted in a significant decrease in BrdU-labeled cells and a 50% decrease after 28 days of alcohol exposure (10).

Doublecortin (DCX) is also used along with BrdU-labelling as a marker for normal migration of neurons into the cerebral cortex and it regulates the organization and stability of microtubules (10). The cells that are usually tagged and marked for proliferation are neural progenitor cells (NPC) found in the hippocampus. NPCs are like stem cells, but specifically the differentiation of progenitor B cells are affected by alcohol exposure (11). The differentiation of progenitor B cells are affected at the late stage of its development due to alcohol intake and other negative effects include lowered activation of transcription factors and cytokine receptors, which furthermore cause a deficit in the survival and growth of the progenitor B cell (11).


Another deficit in the hippocampus due to alcohol exposure is a deficiency in vitamin B1 or thiamine. Vitamin B1 is known to help the body with the digestion process, maintain a healthy liver and help with the proper functioning of the nervous system and brain function. Vitamin B1 is known to be water-soluble (not stored by body) and produced by plants. Since humans do not produce it naturally, it must be ingested through a natural daily diet, which then is used to for ATP (source of cell energy). The gastro-intestinal tract absorbs it, but this pathway can be inhibited by alcohol leading to its deficiency throughout the body (12). Animal studies conductedin Rome have concluded that alcoholics are known to have a deficiency in vitamin B1, which raises the risks of developing the Wernicke–Korsakoff (WK) syndrome (12). Another animal study conducted with rat dams proved that a vitamin B1 deficiency due to induced alcohol exposure during pregnancy caused significant negative effects. There was an increase in fetal death and decrease in litter size when compared to the control group. When the rodents were injected with vitamin B1, the negative effects were reversed, concluding that alcohol played a part in this deficiency and ultimately fetal death (13). There are many other long-term harmful effects on the brain, specifically the hippocampus, but by incorporating the use of biomarkers for future studies, research will prevail on the diagnosis for hippocampal neurodegeneration.

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Figure 5. An MRI of 2 different subjects' brains. normal vs alcoholic showing differences in brain structure

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Figure 4. Difference between levels of brain activity in normal and alcoholic brain






















LATE ONSET OF ALZEIHMER’S DISEASE (LOAD)



As Alzheimer’s disease is known to be prevalent in older aged people due to a decrease in cognitive function because of neuronal degeneration, this can also now be linked to a deficiency in the mitochondrial aldehyde dehydrogenase 2 (ALDH2) gene. ALDH2 is known to be a part of the metabolism pathway of ethanol by the process of acetaldehyde detoxification (3).

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Figure 6. Normal brain vs. LOAD brain
A mutation in this gene (ALDH2*2 allele) causes an increased sensitivity to ethanol, which renders a deficit in the activity of ALDH2. This means that with this deficit in activity, there is a decreased amount of acetaldehyde detoxification, which leads to a toxic buildup. Furthermore, this increases the risk for late-onset Alzheimer’s disease (LOAD) as shown by a study done in Japan (3). This study was comprised of 447 subjects of different sex and age that were studied in order to find how many contained the mutated gene (3). The study also incorporated methods where the mutated gene and the apolipoprotein E4 allele (APOE-e4) where combined in order to study their effects (3). The results concluded that the APOE-e4 allele (known to be a precursor for LOAD) combined with the ALDH2*2 allele caused an increase in the number of people that were affected with LOAD (3). This is a good indication that the deficit in ALDH2 and mutated gene (ALDH2*2) initiates the activation of the LOAD through the exposure of alcohol.

See Also:
http://www.youtube.com/watch?v=9wfnXTmd24U&feature=player_embedded
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Figure 7. Difference in brain structure between normal baby and baby with FAS




FETAL ALCOHOL SYNDROME (FAS)



Fetal Alcohol Syndrome (FAS) is defined as the long-term symptoms that a newborn child is diagnosed with after birth due to prenatal alcohol consumption by the birth mother. Some of these symptoms include mental retardation, behavioral deficits, and slowed growth, physical/facial abnormalities and internal abnormalities (non-functioning kidney and heart) (14). A study conducted in 1957 concluded on the results of 100 subjects, that children born with developmental abnormalities to alcoholic parents were diagnosed with FAS, as prenatal exposure to alcohol poses a severe risk towards FAS (15).
The use of animal models is prevalent in today’s scientific era in order to make precise and controlled predictions through studies conducted, as rodents have similar gestation periods and brain developments to humans (15).

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Figure 8. Physical deficits in child with FAS
As noted from before, alcohol has a significant negative affect on different brain structures including the cerebral cortex, cerebellum and the hippocampus. Harm to these areas of the brain from alcohol exposure cause long-term effects such as neuronal loss, movement, balance and learning abnormalities (15). Research conducted by Edward Riley on rats demonstrated alcohol’s affect during the prenatal period on the offspring that would be born later in time. This study incorporated topics of activity, reactivity and motor differences, avoidance and operant behaviors, sexually dimorphic behaviors and spatial deficits (16). Findings from the study on activity, reactivity and motor differences concluded that rats that were exposed prenatally to alcohol had an increase in activity in an open field test compared to the control group (16). Conclusions on avoidance and operant behaviors stated that the experimental group that was prenatally exposed to alcohol failed the shuttle avoidance test. The shuttle avoidance test involves an animal that must move from one chamber to another chamber with 2 sections in order to avoid a hurtful stimulus (shock) (16). For sexually dimorphic behaviors, evidence proves that prenatal exposure to alcohol caused a change in the sexual behavior of the subject. Rodents that were not exposed to alcohol were found to have a preference for males, whereas rodents that were exposed to alcohol were found to have a preference for males as well (16).


Lastly, rodents exposed to alcohol prenatally depicted spatial deficits. In the study conducted, rodents were given the task to press a bar for a reward (food). Both the control and the experimental (alcohol exposed) groups did this task without error as both bars, when pressed would release a reward. The control group was noticed to use only one of the bars with a specific paw, whereas the experimental group would use both bars interchangeably with both paws (16). Another observation from the study was that when the bars alternated the release of the reward, the experimental group made more mistakes and received less rewards, concluding that they did in fact have a spatial deficit (16). Thus, proving that alcohol intake does in fact produce many negative effects, both short-term and long-term throughout the body.



REFERENCES

  1. Drug and Alcohol Services South Australia. Government of South Australia (2009)
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  3. Ohta S, Ohsawa I, Kamino K, Ando F, Shimokata H. Mitochondrial ALDH2 Deficiency as an Oxidative Stress. Acad. Sci. (2004) **1011**: 36–44
  4. Swahn M, Palmier J. Alcohol. Encyclopedia of Drug Policy. Ed. SAGE (2011) 12-17.
  5. Yeomans M. Alcohol, appetite and energy balance: Is alcohol intake a risk factor for obesity? Physiology & Behaviour (2010) **100**: 82–89
  6. Abernathy K, Chandler J, Woodward J. Alcohol and The Prefrontal Cortex. International Review of Neurobiology. (2010) **91**: 289-320
  7. Lee H, Roh S, Kim D. Alcohol-Induced Blackout. International Journal of Environmental Research and Public Health. (2009) **6**: 2783-2792
  8. Richardson H, Chan S, Crawford E, Lee Y, Funk C, Koob G, Mandyam C. Permanent impairment of birth and survival of cortical and hippocampalproliferating cells following excessive drinking during alcoholdependence Neurobiology of Disease (2009) **36**: 1–10
  9. He J, Overstreet D, Crews F. Abstinence From Moderate Alcohol Self-Administration Alters Progenitor Cell Proliferation and Differentiation in Multiple Brain Regions of Male and Female P Rats. Alcoholism: Clinical and Experimental Research. (2009) **33**: 129-139
  10. Morris S, Eaves D, Smith A, Nixon K. Alcohol Inhibition of Neurogenesis: A Mechanism of Hippocampal Neurodegeneration in an Adolescent Alcohol Abuse Model. Hippocampus. (2010) **20**:596–607
  11. Wang H, Zhou H, Mahler S, Chervenak R, Wolcott M. Alcohol Effects the Late Differentiation of Progenitor B Cells. Alcohol and Alcoholism. (2011) **46**: 26–32
  12. Mancinelli R, Ceccanti M. Biomarkers in Alcohol Misuse: Their Role in the Prevention and Detection of Thiamine Deficiency. Alcohol & Alcoholism. (2009) **44**: 177–182
  13. Ba A. Alcohol and B1 vitamin deficiency-related stillbirths. The Journal of Maternal-Fetal and Neonatal Medicine. (2009) **22**: 452–457
  14. Thomson Healthcare Inc. Fetal alcohol syndrome. Health Reference Center Academic. (2011)
  15. Foltran F, Gregori D, Franchin L, Verduci E, Giovanni M. Effects of Alcohol Consumption in Prenatal Life, Childhood, and Adolescence on Child Development. Nutrition Reveiws. (2011) **69**: 642-659
  16. Riley EP. The Long-Term Behavioral Effects of Prenatal Alcohol Exposure in Rats. Alcoholism: Clinical and Experimental Research (1990) **14**: 670-673


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