Hajszan T, MacLusky NJ, Leranth C. Short-term treatment with the antidepressant fluoxetine triggers pyramidal dendritic spine synapse formation in rat hippocampus. Eur J Neurosci 21: 1299-1303
Department of Obstetrics, Gynaecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, FMB 312, New Haven, CT 06520-8063, USA. European Journal of Neuroscience
(Impact Factor: 3.18).
04/2005; 21(5):1299-303. DOI: 10.1111/j.1460-9568.2005.03968.x
The pathomechanism of major depressive disorder and the neurobiological basis of antidepressant therapy are still largely unknown. It has been proposed that disturbed hippocampal activity could underlie some of the cognitive and vegetative symptoms of depression, at least in part because of loss of pyramidal cell synaptic contacts, a process that is likely to be reversed by antidepressant treatment. Here we provide evidence that daily administration of the antidepressant fluoxetine to ovariectomized female rats for 5 days induces a robust increase in pyramidal cell dendritic spine synapse density in the hippocampal CA1 field, with similar changes appearing in CA3 after 2 weeks of treatment. This rapid synaptic remodelling might represent an early step in the fluoxetine-induced cascade of responses that spread across the entire hippocampal circuitry, leading to the restoration of normal function in the hippocampus. Hippocampal synaptic remodelling might provide a potential mechanism to explain certain aspects of antidepressant therapy and mood disorders, especially those associated with changes in reproductive state in women, that cannot be reconciled adequately with current theories for depression.
Figures in this publication
Available from: Jing Wang
- "administration increases synaptic density in the hippocampal CA1 pyramidal cell layer, and 14 days of treatment has similar effects in the CA3 pyramidal cell layer  . In the olfactory bulbectomy model of depression, chronic treatment with the tricyclic antidepressant amitriptyline blocks the stress-induced decrease in spine density in hippocampal DG, CA1, and CA3 neurons  . "
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ABSTRACT: Depression is a devastating psychiatric disorder widely attributed to deficient monoaminergic signaling in the central nervous system. However, most clinical antidepressants enhance monoaminergic neurotransmission with little delay but require 4-8 weeks to reach therapeutic efficacy, a paradox suggesting that the monoaminergic hypothesis of depression is an oversimplification. In contrast to the antidepressants targeting the monoaminergic system, a single dose of the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine produces rapid (within 2 h) and sustained (over 7 days) antidepressant efficacy in treatment-resistant patients. Glutamatergic transmission mediated by NMDARs is critical for experience-dependent synaptic plasticity and learning, processes that can be modified indirectly by the monoaminergic system. To better understand the mechanisms of action of the new antidepressants like ketamine, we review and compare the monoaminergic and glutamatergic antidepressants, with emphasis on neural plasticity. The pathogenesis of depression may involve maladaptive neural plasticity in glutamatergic circuits that may serve as a new class of targets to produce rapid antidepressant effects.
Neuroscience Bulletin 02/2015; 31(1):75-86. DOI:10.1007/s12264-014-1484-6 · 2.51 Impact Factor
Available from: Avi Peled
- "Electro Convulsive Therapy ECT is also a known effective antidepressant treatment, and increases plasticity . Neuronal death and brain atrophy are also related to depression, for example in dementia . From the theoretical foundations above, the plastic brain is adaptable in the sense that it reduces free energy by executing its Bayesian function of predicting and adapting to incoming stimuli. "
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ABSTRACT: Clinical brain profiling is an attempt to map a descriptive nosology in psychiatry to underlying constructs in neurobiology and brain dynamics. This paper briefly reviews the motivation behind clinical brain profiling (CBP) and presents some provisional validation using clinical assessments and meta-analyses of neuroscientific publications.
The paper has four sections. In the first, we review the nature and motivation for clinical brain profiling. This involves a description of the key aspects of functional anatomy that can lead to psychopathology. These features constitute the dimensions or categories for a profile of brain disorders based upon pathophysiology. The second section describes a mapping or translation matrix that maps from symptoms and signs, of a descriptive sort, to the CBP dimensions that provide a more mechanistic explanation. We will describe how this mapping engenders archetypal diagnoses, referring readers to tables and figures. The third section addresses the construct validity of clinical brain profiling by establishing correlations between profiles based on clinical ratings of symptoms and signs under classical diagnostic categories with the corresponding profiles generated automatically using archetypal diagnoses. We then provide furthervalidation by performing a cluster analysis on the symptoms and signs and showing how they correspond to the equivalent brain profiles based upon clinical and automatic diagnosis.
In the fourth section, we address the construct validity of clinical brain profiling by looking for associations between pathophysiological mechanisms (such as connectivity and plasticity) and nosological diagnoses (such as schizophrenia and depression). Based upon the mechanistic perspective offered in the first section, we test some particular hypotheses about double dissociations using a meta-analysis of PubMed searches. The final section concludes with perspectives for the future and outstanding validation issues for clinical brain profiling.
Medical Hypotheses 10/2014; 83(4). DOI:10.1016/j.mehy.2014.07.013 · 1.07 Impact Factor
Available from: Abolghasem Esmaeili
- ") and synaptogenesis (Geinisman et al., 2001; Hajszan et al., 2005). Synapses are sites of cell–cell contacts that transmit electrical or chemical signals in the brain. "
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ABSTRACT: The number of older people who are suffering from memory impairment is increasing among populations throughout the world. Alzheimer's disease (AD) affects about 5% of people over 65 years old. The hippocampus, a brain area critical for learning and memory, is especially vulnerable to damage in the early stages of AD. Emerging evidence suggests that loss of neurons and synapses are correlated with dementia in this devastating disease. Therefore, neurogenesis and synaptogenesis in adulthood could serve as a preventive as well as a therapeutic target for AD. This study investigated the effect of Rosa damascena extract on neurogenesis and synaptogenesis in an animal model of AD. Molecular, cellular, and behavioral experiments revealed that this treatment could induce neurogenesis and synaptic plasticity and improve memory in AD. Our study suggests that R. damascena is a promising treatment for mild memory impairments and AD. © 2013 Wiley Periodicals, Inc.
Journal of Neuroscience Research 04/2014; 92(4). DOI:10.1002/jnr.23319 · 2.59 Impact Factor
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