Prefrontal cortex Homer expression in an animal model of attention-deficit/hyperactivity disorder.
BACKGROUND
Attention-deficit/hyperactivity disorder (ADHD) is a pervasive neurobehavioral disorder affecting approximately 5% of children and adolescents and 3% of adults, and the prefrontal cortex (PFC) may play the most critical role in the expression of ADHD. Converging previous studies indicate a potential role of Homer--a scaffolding protein family localized at the postsynaptic density (PSD) of glutamatergic excitatory synapses--in behavioral pathologies associated with neuropsychiatric disorders. Accordingly, we speculate that these Homer isoforms might contribute to the etiology and development of ADHD.


METHODS
We investigated the differential mRNA and protein expressions of several Homer isoforms in the PFC of the spontaneous hypertensive rat/Wistar-Kyoto rats (SHR/WKY), the most frequently used animal model of ADHD, using RT-PCR and western blotting. Furthermore, we examined the effects of methylphenidate (MPH) exposure on the behaviors and the expression of different Homer isoforms in the PFC of SHR, using Làt maze, RT-PCR and western blotting, respectively.


RESULTS
Homer 1a and Homer 2a/b, but not Homer 1b/c, were expressed at a significantly lower levels in the PFC of SHR compared with WKY. MPH exposure decreased the locomotor activity and non-selective attention of SHR, and it up regulated the expression of Homer 1a and Homer 2a/b, but not Homer 1b/c, in the PFC of SHR.


CONCLUSIONS
It is plausible that Homer 1a and Homer 2a/b may be involved in the etiology and pathogenesis of ADHD. Future work will focus on elucidating the specific mechanisms of Homer 1a and Homer 2a/b in ADHD.
Hong
Qin
Q
Department of Pediatrics, Nanjing Maternity and Child Health Hospital of Nanjing Medical University, Nanjing 210004, China.
Zhang
Min
M
Pan
Xiao-qin
XQ
Guo
Mei
M
Li
Fei
F
Tong
Mei-ling
ML
Chen
Rong-hua
RH
Guo
Xi-rong
XR
Chi
Xia
X
D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D000072233:Homer Scaffolding Proteins; D008774:Methylphenidate / Q000494:pharmacology / Q000627:therapeutic use; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D020033:Protein Isoforms / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002352:Carrier Proteins; D000697:Central Nervous System Stimulants; D000072233:Homer Scaffolding Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D008774:Methylphenidate