Molecular Psychiatry
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TFEB regulates lysosomal exocytosis of tau and its loss of function exacerbates tau pathology and spreading
Molecular Psychiatry - Tập 26 Số 10 - Trang 5925-5939 - 2021
Strong limbic and weak frontal activation to aggressive stimuli in spouse abusers
Molecular Psychiatry - Tập 13 Số 7 - Trang 655-656 - 2008
Delta-9-tetrahydrocannabinol increases striatal glutamate levels in healthy individuals: implications for psychosis Abstract The neurobiological mechanisms underlying the association between cannabis use and acute or long-lasting psychosis are not completely understood. While some evidence suggests altered striatal dopamine may underlie the association, direct evidence that cannabis use affects either acute or chronic striatal dopamine is inconclusive. In contrast, pre-clinical research suggests that cannabis may affect dopamine via modulation of glutamate signaling. A double-blind, randomized, placebo-controlled, crossover design was used to investigate whether altered striatal glutamate, as measured using proton magnetic resonance spectroscopy, underlies the acute psychotomimetic effects of intravenously administered delta-9-tetrahydrocannabinol (Δ9-THC; 1.19 mg/2 ml), the key psychoactive ingredient in cannabis, in a set of 16 healthy participants (7 males) with modest previous cannabis exposure. Compared to placebo, acute administration of Δ9-THC significantly increased Glutamate (Glu) + Glutamine (Gln) metabolites (Glx) in the left caudate head (P = 0.027). Furthermore, compared to individuals who were not sensitive to the psychotomimetic effects of Δ9-THC, individuals who developed transient psychotic-like symptoms (~70% of the sample) had significantly lower baseline Glx (placebo; P 7= 0.023) and a 2.27-times higher increase following Δ9-THC administration. Lower baseline Glx values (r = −0.55; P = 0.026) and higher previous cannabis exposure (r = 0.52; P = 0.040) were associated with a higher Δ9-THC-induced Glx increase. These results suggest that an increase in striatal glutamate levels may underlie acute cannabis-induced psychosis while lower baseline levels may be a marker of greater sensitivity to its acute psychotomimetic effects and may have important public health implications.
Molecular Psychiatry - Tập 25 Số 12 - Trang 3231-3240 - 2020
Deficits in striatal dopamine release in cannabis dependence
Molecular Psychiatry - Tập 22 Số 1 - Trang 68-75 - 2017
In vivo evidence of lower synaptic vesicle density in schizophrenia
Molecular Psychiatry - Tập 26 Số 12 - Trang 7690-7698 - 2021
Dissociation of functional and structural plasticity of dendritic spines during NMDAR and mGluR-dependent long-term synaptic depression in wild-type and fragile X model mice Abstract Many neurodevelopmental disorders are characterized by impaired functional synaptic plasticity and abnormal dendritic spine morphology, but little is known about how these are related. Previous work in the Fmr1 -/y mouse model of fragile X (FX) suggests that increased constitutive dendritic protein synthesis yields exaggerated mGluR5-dependent long-term synaptic depression (LTD) in area CA1 of the hippocampus, but an effect on spine structural plasticity remains to be determined. In the current study, we used simultaneous electrophysiology and time-lapse two photon imaging to examine how spines change their structure during LTD induced by activation of mGluRs or NMDA receptors (NMDARs), and how this plasticity is altered in Fmr1 -/y mice. We were surprised to find that mGluR activation causes LTD and AMPA receptor internalization, but no spine shrinkage in either wildtype or Fmr1 -/y mice. In contrast, NMDAR activation caused spine shrinkage as well as LTD in both genotypes. Spine shrinkage was initiated by non-ionotropic (metabotropic) signaling through NMDARs, and in wild-type mice this structural plasticity required activation of mTORC1 and new protein synthesis. In striking contrast, NMDA-induced spine plasticity in Fmr1 -/y mice was no longer dependent on acute activation of mTORC1 or de novo protein synthesis. These findings reveal that the structural consequences of mGluR and metabotropic NMDAR activation differ, and that a brake on spine structural plasticity, normally provided by mTORC1 regulation of protein synthesis, is absent in FX. Increased constitutive protein synthesis in FX appears to modify functional and structural plasticity induced through different glutamate receptors.
Molecular Psychiatry - Tập 26 Số 9 - Trang 4652-4669 - 2021
Targeted disruption of serine racemase affects glutamatergic neurotransmission and behavior
Molecular Psychiatry - Tập 14 Số 7 - Trang 719-727 - 2009
Oxidative stress-driven parvalbumin interneuron impairment as a common mechanism in models of schizophrenia
Molecular Psychiatry - Tập 22 Số 7 - Trang 936-943 - 2017
It all sticks together—the APP-related family of proteins and Alzheimer's disease
Molecular Psychiatry - Tập 4 Số 6 - Trang 524-528 - 1999
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