Effect of postnatal methamphetamine trauma and adolescent methylphenidate treatment on adult hippocampal neurogenesis in gerbils

Schaefers, Andrea T.U.; Teuchert-Noodt, Gertraud; Bagorda, Francesco; Brummelte, Susanne

doi:10.1016/j.ejphar.2009.06.006

Cited by 18 publications

(16 citation statements)

References 60 publications

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“…Moreover, Mandyam et al (2008) observed that this drug (0.05 mg/kg/infusion) administered 1 h/day and 6 h/day decreases the number of proliferating cells, characterized by the decreased number of Ki-67-positive cells, a protein expressed during the active phases of the cell cycle. Also, METH induces long-term effects in SGZ stem/progenitor cell proliferation, as described by Schaefers et al (2009) showing that a single METH administration (50 mg/kg) to 14-day-old gerbils decreases the number of BrdU-positive cells, 45 days post-administration. In addition, our group demonstrated that 100 μM METH (48 h of exposure) reduced proliferation in SVZ cultures (Bento et al, 2011).…”

Section: Discussionmentioning

confidence: 88%

Methamphetamine decreases dentate gyrus stem cell self-renewal and shifts the differentiation towards neuronal fate

et al. 2014

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Methamphetamine (METH) is a highly addictive psychostimulant drug of abuse that negatively interferes with neurogenesis. In fact, we have previously shown that METH triggers stem/progenitor cell death and decreases neuronal differentiation in the dentate gyrus (DG). Still, little is known regarding its effect on DG stem cell properties. Herein, we investigate the impact of METH on mice DG stem/progenitor cell self-renewal functions. METH (10nM) decreased DG stem cell self-renewal, while 1nM delayed cell cycle in the G0/G1-to-S phase transition and increased the number of quiescent cells (G0 phase), which correlated with a decrease in cyclin E, pEGFR and pERK1/2 protein levels. Importantly, both drug concentrations (1 or 10nM) did not induce cell death. In accordance with the impairment of self-renewal capacity, METH (10nM) decreased Sox2(+)/Sox2(+) while increased Sox2(-)/Sox2(-) pairs of daughter cells. This effect relied on N-methyl-d-aspartate (NMDA) signaling, which was prevented by the NMDA receptor antagonist, MK-801 (10μM). Moreover, METH (10nM) increased doublecortin (DCX) protein levels consistent with neuronal differentiation. In conclusion, METH alters DG stem cell properties by delaying cell cycle and decreasing self-renewal capacities, mechanisms that may contribute to DG neurogenesis impairment followed by cognitive deficits verified in METH consumers.

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Section: Discussionmentioning

confidence: 88%

Methamphetamine decreases dentate gyrus stem cell self-renewal and shifts the differentiation towards neuronal fate

et al. 2014

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“…GFAP glial fibrillary acidic protein, MPH methylphenidate treated with MPH (2 mg/kg twice a day for 15 days) showed a decrease in survival of new cells of the hippocampus, without altering cell proliferation. In addition, Schaeffer et al [54] reported that chronic treatment with MPH (5 mg/kg for 30 days) did not alter the number of proliferating cells. In contrast, it recently reported an increase in cell proliferation and differentiation of neuroblasts after MPH administration (10 mg/kg once daily for 28 days) [55].…”

Section: Discussionmentioning

confidence: 96%

Methylphenidate Causes Behavioral Impairments and Neuron and Astrocyte Loss in the Hippocampus of Juvenile Rats

et al. 2016

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Although the use, and misuse, of methylphenidate is increasing in childhood and adolescence, there is little information about the consequences of this psychostimulant chronic use on brain and behavior during development. The aim of the present study was to investigate hippocampus biochemical, histochemical, and behavioral effects of chronic methylphenidate treatment to juvenile rats. Wistar rats received intraperitoneal injections of methylphenidate (2.0 mg/kg) or an equivalent volume of 0.9 % saline solution (controls), once a day, from the 15th to the 45th day of age. Results showed that chronic methylphenidate administration caused loss of astrocytes and neurons in the hippocampus of juvenile rats. BDNF and pTrkB immunocontents and NGF levels were decreased, while TNF-α and IL-6 levels, Iba-1 and caspase 3 cleaved immunocontents (microglia marker and active apoptosis marker, respectively) were increased. ERK and PKCaMII signaling pathways, but not Akt and GSK-3β, were decreased. SNAP-25 was decreased after methylphenidate treatment, while GAP-43 and synaptophysin were not altered. Both exploratory activity and object recognition memory were impaired by methylphenidate. These findings provide additional evidence that early-life exposure to methylphenidate can have complex effects, as well as provide new basis for understanding of the biochemical and behavioral consequences associated with chronic use of methylphenidate during central nervous system development.

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“…24 It is noteworthy that few studies have addressed the effect of METH on neurogenesis, 23,40,41 and indeed, little is known about the effect of METH on stem/progenitor cells toxicity and capacity of neuronal differentiation, especially in the SVZ. Thus, the present work was undertaken to fill this gap.…”

Section: Discussionmentioning

confidence: 98%

Methamphetamine Exerts Toxic Effects on Subventricular Zone Stem/Progenitor Cells and Inhibits Neuronal Differentiation

Bento

Baptista²,

Malva³

et al. 2011

Rejuvenation Research

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Methamphetamine (METH) is a potent and widely consumed psychostimulant drug that causes brain functional and structural abnormalities. However, there is little information regarding METH impact on adult neurogenic niches and, indeed, nothing is known about its consequences on the subventricular zone (SVZ). Thus, this work aims to clarify the effect of METH on SVZ stem/progenitor cells dynamics and neurogenesis. For that purpose, SVZ neurospheres were obtained from early postnatal mice and treated with increasing concentrations of METH (1 μM to 500 μM). Exposure to 100, 250, or 500 μM METH for 24 h triggered cell death both by necrosis and apoptosis, as assessed by propidium iodide uptake, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and quantification of the proapoptotic caspase-3 activity. Furthermore, we showed that METH inhibited SVZ progenitor cells proliferation as it decreased BrdU incorporation. Interestingly, at non-toxic concentrations (1 and 10 μM), METH decreased neuronal differentiation and maturation, which were evaluated by quantification of the number of neuronal nuclei-positive neurons and measurements of phospho-c-Jun-NH(2)-terminal kinase signal in growing axons, respectively. Altogether, our data demonstrate that METH has a negative impact on SVZ stem/progenitor cells, inducing cell death and inhibiting neurogenesis, effects that in vivo may challenge the cell replacement capacities displayed by endogenous populations of brain stem/progenitor cells.

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Effect of postnatal methamphetamine trauma and adolescent methylphenidate treatment on adult hippocampal neurogenesis in gerbils

Cited by 18 publications

References 60 publications

Methamphetamine decreases dentate gyrus stem cell self-renewal and shifts the differentiation towards neuronal fate

Methamphetamine decreases dentate gyrus stem cell self-renewal and shifts the differentiation towards neuronal fate

Methylphenidate Causes Behavioral Impairments and Neuron and Astrocyte Loss in the Hippocampus of Juvenile Rats

Methamphetamine Exerts Toxic Effects on Subventricular Zone Stem/Progenitor Cells and Inhibits Neuronal Differentiation

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