Is hippocampal atrophy a future drug target?
Abstract
Hippocampus is the brain structure, vital for episodic and declarative memory. Atrophy of the human hippocampus is seen in a variety of psychiatric and neurological disorders e.g. recurrent depression, schizophrenia, bipolar disorder, post-traumatic stress disorder, epilepsy, head injury, and Alzheimer's disease (AD). Importantly, aging hippocampus also undergoes atrophy. In many instances, for example, AD, the atrophy precedes the development of symptoms while in others, there is a temporal relationship between atrophy and symptomatology. The presence of atrophied hippocampus is one of the most consistent features of many common psychiatric disorders. Several factors contribute to this atrophy. Stress is one of the most profound factors implicated and the mechanisms involve glucocorticoids, serotonin, excitatory amino acids etc. Hippocampal formation as a whole can undergo atrophy or its individual structural components e.g. apical dendrities can exhibit atrophy. Several drugs of unrelated classes have been shown to prevent atrophy indicating heterogenous manner in which hippocampal atrophy is produced. These include, tianeptine (affects structural plasticity in hippocampus and is an effective antidepressant); phenytoin (antiseizure and neuroprotective); fluoxetine (downregulates neurodegenerative enzyme and increases neuroprotective hippocampal S100 beta); lithium (neuroprotective and antiapoptotic); tricyclic antidepressants (increase hippocampal neurogenesis); antipsychotics (reduce hippocampal neuronal suppression); sodium valproate (increases neurogenesis) and mifepristone (antioxidant, neuroprotective and anti-glucocorticoid). Now the most important question is: to what extent does the hippocampal atrophy play a role in the genesis of symptoms of diseases or their progression? And if it does, can we achieve the same degree of prevention or reversal seen in experimental animals, in humans also. An even more important question is: whether the prevention of atrophy would be clinically useful in affecting disease, viz slowing its progression, reducing morbidity, complications or positively affecting the outcome of one or more of its clinically important aspects. If the answer to this is yes, we would have to know at what stage of the disease we use the drugs, dose, duration, follow-up and efficacy. The use of these drugs in the above mentioned conditions can not only test the potential of atrophy as a future drug target, but could also help in learning more about the hippocampus in both health and diseases.
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Reduced hippocampal volume is observed in patients diagnosed with mood disorders, post-traumatic stress disorder, schizophrenia and Alzheimer's Disease.
“For instance, reduced hippocampal volume is observed in patients diagnosed with mood disorders, post-traumatic stress disorder (PTSD), schizophrenia and Alzheimer's Disease (98).”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [98]
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Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age
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- Authors
- Dhikav, V., & Anand, K. S.
- Affiliations
- All India Institute of Medical Sciences (IN)
- Post Graduate Institute of Medical Education and Research (IN)
- Corresponding author
- Dhikav, Vikas
- ORCID
- Dhikav, Vikas
- Venue
- Medical Hypotheses
- Publisher
- Elsevier BV
- Published
- 2007-01
- Volume
- 68
- Issue
- 6
- Pages
- 1300-1306
- ISSN
- 0306-9877 (ISSN-L)
- OpenAlex
- W2037750401
- Cited by
- 63
- References
- 47
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 4 · 2022: 5 · 2021: 4 · 2019: 1 · 2018: 3 · 2017: 3 · 2016: 3 · 2014: 1 · 2013: 2 · 2012: 5
- FWCI
- 1.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Medical Hypotheses (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- hippocampal atrophy, therapeutic target, neuroprotection, hippocampal neurogenesis, Alzheimer's disease, stress, glucocorticoids, antidepressants, antipsychotic drugs, lithium, mifepristone, valproic acid, tianeptine, phenytoin, fluoxetine, tricyclic antidepressants
- MeSH terms
- Atrophy, Pharmaceutical Preparations, Forecasting, Hippocampus, Humans, Models, Biological, Drug Delivery Systems
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