Regulation of hippocampal gene expression is conserved in two species subjected to different stressors and antidepressant treatments.
BACKGROUND
Chronic stress has significant effects on hippocampal structure and function. We have previously identified nerve growth factor (NGF), membrane glycoprotein 6a (M6a), the guanine nucleotide binding protein (G protein) alpha q polypeptide (GNAQ), and CDC-like kinase 1 (CLK-1) as genes regulated by psychosocial stress and clomipramine treatment in the hippocampus of tree shrews. These genes encode proteins involved in neurite outgrowth.


METHODS
To analyze whether regulation of the above-mentioned genes is conserved between different species, stressors, and antidepressant drugs, we subjected mice to repeated restraint stress and tianeptine treatment and measured hippocampal messenger RNA (mRNA) levels by real time reverse transcription polymerase chain reaction (RT-PCR).


RESULTS
Chronically stressed mice displayed a reduction in transcript levels for NGF, M6a, GNAQ, and CLK-1. In addition, other genes implicated in neuronal plasticity, such as brain-derived neurotrophic factor (BDNF), cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), protein kinase C (PKC), neural cell adhesion molecule (NCAM), and synapsin I were downregulated in stressed mice. Tianeptine treatment reversed the stress effects for the genes analyzed. Alterations in gene expression were dependent on the duration of the stress treatment and, in some cases, were only observed in male mice.


CONCLUSIONS
These results suggest that genes involved in neurite remodeling are one of the main targets for regulation by chronic stress. The finding that this regulation is conserved in different stress models and antidepressant treatments highlights the biological relevance of the genes analyzed and suggests that they might be involved in stress-related disorders.
Alfonso
Julieta
J
IIB-INTECH-Universidad Nacional de Gral, San Martin, Argentina. julialfo@iib.unsam.edu.ar
Frick
Luciana R
LR
Silberman
Dafne M
DM
Palumbo
María L
ML
Genaro
Ana M
AM
Frasch
Alberto C
AC
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D005260:Female; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D005838:Genotype; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D020932:Nerve Growth Factor / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D013315:Stress, Psychological / Q000150:complications* / Q000473:pathology; D026801:Synteny / Q000187:drug effects / Q000235:genetics*; D013841:Thiazepines / Q000494:pharmacology*; D000099317:Hippo Kinases
D000928:Antidepressive Agents; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D008562:Membrane Glycoproteins; D020932:Nerve Growth Factor; D009419:Nerve Tissue Proteins; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D013841:Thiazepines; C083480:Gpm6a protein, mouse; C050504:tianeptine; C402650:SLK protein, mouse; D000099317:Hippo Kinases