Stress and hippocampal abnormalities in psychiatric disorders

Sala, Michela; Pérez, Jorge; Soloff, Paul H.; Nemi, Stefania Ucelli Di; Caverzasi, Edgardo; Soares, Jair C.; Brambilla, Paolo

doi:10.1016/j.euroneuro.2003.12.005

Cited by 145 publications

(88 citation statements)

References 151 publications

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“…We chose these brain areas because the PFC and hippocampus play important roles in mood regulation (George et al, 1994) and cognition (Sweatt, 2004), respectively, and have been implicated in suicide (Rajkowska, 1997;Dwivedi et al, 2003aDwivedi et al, , 2005aDwivedi et al, , 2006. Moreover, the hippocampus is the primary brain area affected by stress (Sala et al, 2004), one of the major factors in suicidal behavior (Clayton, 1985;Monk, 1987). We selected the cerebellum because this brain area is largely unaffected in depression and suicide.…”

Section: Introductionmentioning

confidence: 99%

Lower Phosphoinositide 3-Kinase (PI 3-kinase) Activity and Differential Expression Levels of Selective Catalytic and Regulatory PI 3-Kinase Subunit Isoforms in Prefrontal Cortex and Hippocampus of Suicide Subjects

Dwivedi

Rizavi

Teppen

et al. 2007

Neuropsychopharmacol

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Phosphoinositide 3 (PI 3)-kinase is one of the key signaling enzymes that participates in a myriad of physiological functions in brain and is utilized by neurotrophins to mediate neuronal plasticity, cell survival, and inhibition of apoptosis for several neuronal subtypes. Our recent demonstration that expression of neurotrophic factors and activation of the receptor tyrosine kinase B are significantly altered in postmortem brain of suicide subjects led us to examine whether suicide brain is associated with alterations in PI 3-kinase signaling. In prefrontal cortex (PFC), hippocampus, and cerebellum of suicide (n ¼ 28) and nonpsychiatric control (n ¼ 21) subjects we examined catalytic activation of PI 3-kinase, and mRNA and protein levels of regulatory (p85a, p85b) and catalytic (p110a, p110b) subunits of PI 3-kinase. It was observed that the catalytic activity of PI 3-kinase was significantly reduced in PFC and hippocampus of suicide subjects compared with nonpsychiatric control subjects. Competitive PCR analysis revealed significantly reduced mRNA expression of p85b and p110a and increased expression of p85a subunit isoforms in PFC and hippocampus of suicide subjects. Alterations in these catalytic and regulatory subunits were accompanied by changes in their respective protein levels. These changes were not present in cerebellum of suicide subjects. Also, these changes were present in all suicide subjects irrespective of psychiatric diagnosis. Our findings of reduced activation and altered expression of specific PI 3-kinase regulatory and catalytic subunit isoforms demonstrate abnormalities in this signaling pathway in postmortem brain of suicide subjects and suggest possible involvement of aberrant PI 3-kinase signaling in the pathogenic mechanisms of suicide.

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Section: Introductionmentioning

confidence: 99%

Lower Phosphoinositide 3-Kinase (PI 3-kinase) Activity and Differential Expression Levels of Selective Catalytic and Regulatory PI 3-Kinase Subunit Isoforms in Prefrontal Cortex and Hippocampus of Suicide Subjects

Dwivedi

Rizavi

Teppen

et al. 2007

Neuropsychopharmacol

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“…In addition to changes to cell proliferation, impaired maturation of adult-born dentate granule cells in patients with schizophrenia has also been reported ). Interestingly, several studies show a correlation between amelioration of the behavioral and cognitive symptoms of schizophrenia and normalization of hippocampal volume, thus linking the anatomical and cognitive behavioral manifestations of this disorder to the hippocampus (Sapolsky 2000;Sala et al 2004;Dhikav and Anand 2007). Impaired adult hippocampal neurogenesis, as a distinct form of dysregulated neurodevelopment, might contribute to the structural changes and hippocampal-dependent affective and cognitive symptoms.…”

Section: Neurodevelopmental Model Of Schizophreniamentioning

confidence: 99%

“…Hippocampal volume reduction represents a loss of gray matter, which could lead to memory deficits and impaired cognitive functions (Goldman and Mitchell 2004). Intriguingly, these structural and functional changes of the hippocampus in patients with psychiatric disorders can be attenuated or even reversed by treating patients with antidepressants, antipsychotics, or increasing physical exercise, many of which are known to have a profound impact on hippocampal neurogenesis (Sala et al 2004;Dhikav and Anand 2007;Kempermann et al 2010;Erickson et al 2014).…”

mentioning

confidence: 99%

Adult Neurogenesis and Psychiatric Disorders

Kang

Wen

Song

et al. 2016

Cold Spring Harb Perspect Biol

160

118

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Psychiatric disorders continue to be among the most challenging disorders to diagnose and treat because there is no single genetic or anatomical locus that is causative for the disease. Current treatments are often blunt tools used to ameliorate the most severe symptoms, at the risk of disrupting functional neural systems. There is a critical need to develop new therapeutic strategies that can target circumscribed functional or anatomical domains of pathology. Adult hippocampal neurogenesis may be one such domain. Here, we review the evidence suggesting that adult hippocampal neurogenesis plays a role in emotional regulation and forms of learning and memory that include temporal and spatial memory encoding and context discrimination, and that its dysregulation is associated with psychiatric disorders, such as affective disorders, schizophrenia, and drug addiction. Further, adult neurogenesis has proven to be an effective model to investigate basic processes of neuronal development and converging evidence suggests that aberrant neural development may be an etiological factor, even in late-onset diseases. Constitutive neurogenesis in the hippocampus of the mature brain reflects large-scale plasticity unique to this region and could be a potential hub for modulation of a subset of cognitive and affective behaviors that are affected by multiple psychiatric disorders.

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“…Hippocampus is also important in "memory consolidation" which is the process of conversion of short-term memory to longterm memory in the neocortex. Here, hippocampus plays a critical role in supplying the first input necessary for the longterm memory, conversion of these to long-term memories, and formation and strenghtening of the synaptic connections necessary for the maintenance of long-term memory (18,23). Extensive degenerative changes have been reported in the hippocampus and cortex of patients with AD.…”

Section: Pathophysiological Basis Of Admentioning

confidence: 99%

“…Many studies on human and animals conclude that hippocampus is an important brain region involved in memory formation (17,18). The amy-gdala and the orbitofrontal cortex are important contributors of information processing and formation of declarative memory (19,20).…”

Section: Pathophysiological Basis Of Admentioning

confidence: 99%

Alzheimer disease and neuroplasticity: New approaches and new targets in pharmacotherapy

Uzbay¹

2012

mpj

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Stress and hippocampal abnormalities in psychiatric disorders

Cited by 145 publications

References 151 publications

Lower Phosphoinositide 3-Kinase (PI 3-kinase) Activity and Differential Expression Levels of Selective Catalytic and Regulatory PI 3-Kinase Subunit Isoforms in Prefrontal Cortex and Hippocampus of Suicide Subjects

Lower Phosphoinositide 3-Kinase (PI 3-kinase) Activity and Differential Expression Levels of Selective Catalytic and Regulatory PI 3-Kinase Subunit Isoforms in Prefrontal Cortex and Hippocampus of Suicide Subjects

Adult Neurogenesis and Psychiatric Disorders

Alzheimer disease and neuroplasticity: New approaches and new targets in pharmacotherapy

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