Biomedical subjects

Kim Fejgin

Publications and source records attributed to Kim Fejgin.

4 recordsLinked to original sources

PubMed2021

1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans.

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.

Brain↗

PubMed2006

Phencyclidine affects memory in a nitric oxide-dependent manner: working and reference memory.

Phencyclidine (PCP), a non-competitive NMDA receptor antagonist, was used to model schizophrenia-like cognitive dysfunctions of learning and memory in rats using the Morris water maze model for spatial memory. A protocol introduced by Baldi and co-workers was used to distinguish working memory from reference memory. Male Sprague-Dawley rats were administered PCP (2.0 mg/kg) before the first swimming trial on each of five spatial memory acquisition days, either alone or after pre-treatment with the nitric oxide synthase inhibitor, L-NAME (10 mg/kg). Probe tests for memory were conducted before and after each acquisition session. The results showed that PCP disrupted the acquisition of both working and reference memory. Pre-treatment with L-NAME reversed both these effects of PCP. L-NAME treatment by itself did not significantly alter either acquisition or retention of spatial memory.

Analysis of Variance↗

PubMed2006

Effects of phencyclidine on spatial learning and memory: nitric oxide-dependent mechanisms.

Cognitive deficits of schizophrenia constitute a disabling part of the disease predicting treatment success as well as functional outcome. Phencyclidine (PCP), a non-competitive NMDA receptor antagonist was used to model schizophrenic cognitive dysfunctions of learning and memory using the Morris water maze paradigm for reference memory. In experiment 1 male Sprauge-Dawley rats were acutely administered PCP (0.5, 1.0 and 2.0 mg/kg s.c.) before the first swim session on each of the four acquisition days. Probe test for reference memory was performed 2 days after the last acquisition day; the first probe without drug treatment to assess reference memory and a second probe with prior drug treatment to control for state dependency effects of PCP. In experiment 2 the effects of pre-treatment (10 min before PCP) with the nitric oxide synthase inhibitor, L-NAME (10 mg/kg s.c.), on the PCP (2 mg/kg)-induced spatial memory deficit was evaluated in the Morris water maze paradigm for reference memory. The results showed that PCP in a dose of 2 mg/kg disrupts spatial learning as estimated by prolonged search time to find platform during acquisition as well as the reference memory test as measured by less time spent in target quadrant during probe trial. No state dependency effects of PCP were found. Pre-treatment with L-NAME completely reversed the PCP-induced disruption of acquisition learning. The reference memory disruption was, however, not completely restored as measured by probe trial.

Analysis of Variance↗

PubMed2004

Activation of a nitric-oxide-sensitive cAMP pathway with phencyclidine: elevated hippocampal cAMP levels are temporally associated with deficits in prepulse inhibition.

RATIONALE: Schizophrenic patients show deficits in pre-attentive information processing as evidenced, for example, by disrupted prepulse inhibition, a measure of sensorimotor gating. A similar disruption can be observed in animals treated with the psychotomimetic agent, phencyclidine (PCP). However, the mechanism by which PCP alters brain function has not been fully elucidated. Recent studies have demonstrated that certain behavioural and neurochemical effects of PCP in rats and mice are blocked by nitric oxide (NO) synthase inhibition, suggesting an important role for NO in the effects of PCP. OBJECTIVE: The aim of the present study was to investigate the effects of PCP on cAMP production in the ventral hippocampus and the role of NO in these effects using in vivo microdialysis in rats. Furthermore, the effects of PCP on acoustic startle reactivity and prepulse inhibition of acoustic startle were compared with changes in cAMP levels in the ventral hippocampus. RESULTS: Significant increases in cAMP levels were observed in the ventral hippocampus following both local infusion (10(-4) mol/l and 10(-3) mol/l) and systemic administration (2 mg/kg) of PCP. The PCP-induced changes in prepulse inhibition and startle reactivity were associated in magnitude and duration with the increase in cAMP levels in the hippocampus. Furthermore, systemic administration of the NO synthase inhibitor, L: -NAME (10 mg/kg), blocked both the changes in cAMP levels and the behavioural responses induced by PCP. CONCLUSIONS: These findings indicate that the effects of PCP on prepulse inhibition and startle reactivity are associated with an increase in cAMP levels in the ventral hippocampus, and that this change in cAMP response may be linked to the production of NO.

Acoustic Stimulation↗