Methamphetamine Causes Differential Alterations in Gene Expression and Patterns of Histone Acetylation/Hypoacetylation in the Rat Nucleus Accumbens

Methamphetamine (METH) addiction is associated with several neuropsychiatric symptoms. Little is known about the effects of METH on gene expression and epigenetic modifications in the rat nucleus accumbens (NAC). Our study investigated the effects of a non-toxic METH injection (20 mg/kg) on gene expression, histone acetylation, and the expression of the histone acetyltransferase (HAT), ATF2, and of the histone deacetylases (HDACs), HDAC1 and HDAC2, in that structure. Microarray analyses done at 1, 8, 16 and 24 hrs after the METH injection identified METH-induced changes in the expression of genes previously implicated in the acute and longterm effects of psychostimulants, including immediate early genes and corticotropin-releasing factor (Crf). In contrast, the METH injection caused time-dependent decreases in the expression of other genes including Npas4 and cholecystokinin (Cck). Pathway analyses showed that genes with altered expression participated in behavioral performance, cell-to-cell signaling, and regulation of gene expression. PCR analyses confirmed the changes in the expression of c-fos, fosB, Crf, Cck, and Npas4 transcripts. To determine if the METH injection caused post-translational changes in histone markers, we used western blot analyses and identified METH-mediated decreases in histone H3 acetylated at lysine 9 (H3K9ac) and lysine 18 (H3K18ac) in nuclear sub-fractions. In contrast, the METH injection caused time-dependent increases in acetylated H4K5 and H4K8. The changes in histone acetylation were accompanied by decreased expression of HDAC1 but increased expression of HDAC2 protein levels. The histone acetyltransferase, ATF2, showed significant METH-induced increased in protein expression. These results suggest that METH-induced alterations in global gene expression seen in rat NAC might be related, in part, to METH-induced changes in histone acetylation secondary to changes in HAT and HDAC expression. The causal role that HATs and HDACs might play in METH-induced gene expression needs to be investigated further

Découverte originale dans le système nerveux central et l'hypophyse d'hormones peptidiques uniquement connues dans l'appareil digestif: les peptides de la famille gastrine-cholecystokinine

Doctorat en sciences médicalesinfo:eu-repo/semantics/nonPublishe

Neurophysiologie humaine

SYL-002229 et SYL-002249 = Première partiePremière partie :Neurophysiologie cellulaire et moléculaire Illustrations :1 à 15 -- SYL-5130 ;Neurophysiologie cellulaire et moléculaire :Illustrations :16 à 201re édition 1993-1994/13e Candidature Médecineinfo:eu-repo/semantics/published

Découverte originale dans le système nerveux central et l'hypophyse d'hormones peptidiques uniquement connues dans l'appareil digestif: les peptides de la famille gastrine-cholecystokinine

Doctorat en sciences médicalesinfo:eu-repo/semantics/nonPublishe

Cholecystokinins in the central nervous system

SCOPUS: NotDefined.jinfo:eu-repo/semantics/publishe

Correlation between ultrastructure and histochemistry of lafora bodies

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Physiologie et physiopathologie du système nerveux et des organes des sens

2e édition 1998-1999/13e Candidature Médecineinfo:eu-repo/semantics/published

Transient neurotensin in the human inferior olive during development

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Cholecystokinin receptors of A type in the human dorsal medulla oblongata and meningiomas, and of B type in small cell lung carcinomas

Cholecystokinin receptors of the pancreatic type (A type) were found in the infant and adult human area postrema, medial nucleus tractus solitarius, vagus dorsal motor nucleus and in the meningiomas, and of the brain type (B type) in the ventral nucleus tractus solitarius and in the small cell lung carcinomas.SCOPUS: ar.jinfo:eu-repo/semantics/publishe