Lesions of hippocampal circuitry define synaptosomal-associated protein-25 (SNAP-25) as a novel presynaptic marker

Geddes, James W.; Hess, E.J.; Hart, Roger A.; Kesslak, J. Patrick; Cotman, Carl W.; Wilson, Michael C.

doi:10.1016/0306-4522(90)90047-8

Cited by 85 publications

(40 citation statements)

References 21 publications

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“…His group found significantly decreased SNAP-25 levels at 3 days post-injury followed by increasing levels to 75% of baseline at day 18. Consistent with this process are observations of Geddes et al, which demonstrated increased SNAP-25 in brain regions adjacent to deafferented areas athat had reduced SNAP (Geddes et al 1990). Possibly, our CSF SNAP-25 level, which measures the extracellular compartment, is the mirror image of Jorgensen's and Geddes's intracellular brain homogenate SNAP-25 levels.…”

supporting

confidence: 72%

CSF SNAP-25 in Schizophrenia and Bipolar Illness A Pilot Study

Thompson

1999

Neuropsychopharmacology

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Research efforts to identify and understand the In the past 20 years, scientists have conducted extensive research to identify the pathology and etiology of schizophrenia and bipolar illness. In schizophrenic subjects, neuroimaging and functional analysis has identified abnormalities in various brain structures (Nasrallah 1990). Neuropathological studies of schizophrenics have revealed brain changes ranging from loss of gray matter to disorganization of the normal neuronal architecture (Bloom 1993). More recently, changes in vesicular-and growth-associated proteins have been identified in post-mortem brains of schizophrenics (Barbeau et al. 1995;Browning et al. 1993;Eastwood et al. 1995;Perrone-Bizzozero et al. 1996). Based on the accumulated clinical and laboratory information, investigators have developed two models to explain the pathophysiology of schizophrenia.The neurodegeneration hypothesis proposes that schizophrenia is the result of degeneration or loss of neurons, similar to Alzheimer's disease. This hypothesis dates to 1919, when schizophrenia was referred to as "dementia praecox" (Kraepelin 1919). However, postmortem studies have not consistently identified evidence of abnormal neurodegeneration in schizophrenic brains (Arnold et al. 1991).An alternative hypothesis states that the pathology Received November 24, 1998; revised April 8, 1999; accepted June 7, 1999. 718 P.M. Thompson et al. N EUROPSYCHOPHARMACOLOGY 1999 -VOL . 21 , NO . 6 of schizophrenia arises during embryonic and fetal developmental (Bloom 1993;Saugstad 1989). In this hypothesis, Weinberger (Weinberger 1987) proposes that a static brain lesion is established early in development and that neurodegeneration is not a major factor in the adult pathology. As the brain matures, it compensates for the lesion until the adaptations are overwhelmed. When the brain adaptions are insufficient to compensate, the final groups of behavioral symptoms are collectively described as schizophrenia. As in the neurodegenerative hypothesis, supporting data are circumstantial (Raedler et al. 1998).In bipolar illness, less is known about brain pathology than with schizophrenia. Consistent findings include mood state-dependent changes in erythrocyte Na-K-ATPase activity (Looney and el-Mallakh 1997) and an increased risk for structural brain abnormalities (Altshuler et al. 1995). Both types of studies may indicate subtle neuronal damage. A question raised by both schizophrenia and bipolar studies is whether there is ongoing neuronal damage or degeneration.The direct approach to test the hypothesis that schizophrenia and bipolar illness are not associated with ongoing neurodegeneration is to study neuronal tissue from living patients. However, moral and ethical restrictions eliminate this type of study. One way to bypass this limitation is to study a protein that has been demonstrated to be involved with the adult post-mortem pathology and can be measured in living subjects. Synaptosomal-associated protein 25kDa (SNAP-25) is a candidate protein for th...

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supporting

confidence: 72%

CSF SNAP-25 in Schizophrenia and Bipolar Illness A Pilot Study

Thompson

1999

Neuropsychopharmacology

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“…1D) and PN22-24 (data not shown) mice revealed no apparent neuroanatomical abnormalities, and particularly no morphological deficits in hippocampal formation were apparent. Furthermore, immunohistological staining demonstrated comparable accumulation of SNAP-25 in presynaptic mossy fiber terminals, a characteristic of SNAP-25 expression (Oyler et al, 1989;Geddes et al, 1990), again suggesting that hippocampal development and morphogenesis are not greatly impaired.…”

Section: Generation Of Mice With a Targeted Insertion Of Tkneo In Thementioning

confidence: 85%

Developmentally Regulated Switch in Alternatively Spliced SNAP-25 Isoforms Alters Facilitation of Synaptic Transmission

Bark¹,

Bellinger²,

Kaushal³

et al. 2004

J. Neurosci.

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Although the basic molecular components that promote regulated neurotransmitter release are well established, the contribution of these proteins as regulators of the plasticity of neurotransmission and refinement of synaptic connectivity during development is elaborated less fully. For example, during the period of synaptic growth and maturation in brain, the expression of synaptosomal protein 25 kDa (SNAP-25), a neuronal t-SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) essential for action potentialdependent neuroexocytosis, is altered through alternative splicing of pre-mRNA transcripts. We addressed the role of the two splicevariant isoforms of SNAP-25 with a targeted mouse mutation that impairs the shift from SNAP-25a to SNAP-25b. Most of these mutant mice die between 3 and 5 weeks of age, which coincides with the time when SNAP-25b expression normally reaches mature levels in brain and synapse formation is essentially completed. The altered expression of these SNAP-25 isoforms influences short-term synaptic function by affecting facilitation but not the initial probability of release. This suggests that mechanisms controlling alternative splicing between SNAP-25 isoforms contribute to a molecular switch important for survival that helps to guide the transition from immature to mature synaptic connections, as well as synapse regrowth and remodeling after neural injury.

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“…[8][9][10][11][12][13][14][15] The synaptosomalassociated protein of 25 kDa (SNAP-25) gene lies in an area of previous suggestive linkage to intelligence (20p12-p11.2), 3 and is highly expressed by neurons in the hippocampus. [16][17][18] The SNAP-25 gene product is a presynaptic plasma membrane protein that is an integral component of the vesicle docking and fusion machinery that regulates neurotransmitter release. 17,19,20 It is also implicated in axonal growth and synaptic plasticity.…”

Section: Introductionmentioning

confidence: 99%

The SNAP-25 gene is associated with cognitive ability: evidence from a family-based study in two independent Dutch cohorts

et al. 2006

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The synaptosomal-associated protein of 25 kDa (SNAP-25) gene plays an integral role in synaptic transmission, and is differentially expressed in the mammalian brain in the neocortex, hippocampus, anterior thalamic nuclei, substantia nigra and cerebellar granular cells. Recent studies have suggested a possible involvement of SNAP-25 in learning and memory, both of which are key components of human intelligence. In addition, the SNAP-25 gene lies in a linkage area implicated previously in human intelligence. In two independent family-based Dutch samples of 391 (mean age 12.4 years) and 276 (mean age 37.3 years) subjects, respectively, we genotyped 12 single-nucleotide polymorphisms (SNPs) in the SNAP-25 gene on 20p12-20p11.2. From all individuals, standardized intelligence measures were available. Using a family-based association test, a strong association was found between three SNPs in the SNAP-25 gene and intelligence, two of which showed association in both independent samples. The strongest, replicated association was found between SNP rs363050 and performance IQ (PIQ), where the A allele was associated with an increase of 2.84 PIQ points (P = 0.0002). Variance in this SNP accounts for 3.4 % of the phenotypic variance in PIQ.

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Lesions of hippocampal circuitry define synaptosomal-associated protein-25 (SNAP-25) as a novel presynaptic marker

Cited by 85 publications

References 21 publications

CSF SNAP-25 in Schizophrenia and Bipolar Illness A Pilot Study

CSF SNAP-25 in Schizophrenia and Bipolar Illness A Pilot Study

Developmentally Regulated Switch in Alternatively Spliced SNAP-25 Isoforms Alters Facilitation of Synaptic Transmission

The SNAP-25 gene is associated with cognitive ability: evidence from a family-based study in two independent Dutch cohorts

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