Spontaneously hypertensive rats: further evaluation of age-related memory performance and cholinergic marker expression.
OBJECTIVE
The spontaneously hypertensive rat (SHR), often used to study cardiovascular disease processes, may also be utilized to model certain central nervous system changes associated with memory disorders. Previous work in our laboratory indicated that central nicotinic acetylcholine receptors are markedly diminished and that memory-related task performance is impaired in this rodent phenotype. Due to the well-documented importance of the central cholinergic system to memory processes and its vulnerability to the effects of aging, it was of interest to measure other cholinergic markers and to further evaluate memory function in older SHRs.


METHODS
Radial arm maze performance was used to assess working memory, quantitative receptor autoradiography with [3H]-pirenzipine, [3H]-AFDX-384 and [3H]-epibatidine (combined with cytisine) was used to determine the densities of muscarinic-M1 and -M2 and nicotinic cholinergic alpha3 receptors, respectively. Immunoblotting experiments were also used to determine the expression of the presynaptic cholinergic markers, choline acetyltransferase and the vesicular acetylcholine transporter.


RESULTS
Radial arm maze performance was impaired in hypertensive (compared with normotensive Wistar and Wistar-Kyoto) rats, regardless of age. M1 binding was increased in frontal and prefrontal cortical areas in SHR (p < 0.05), whereas M2 densities were higher in the hypertensive phenotype in the caudate putamen. A lower expression of alpha3-containing nicotinic receptors was observed in the superior colliculus in SHRs. Age-related differences in the expression of the vesicular acetylcholine transporter were noted in the hippocampus.


CONCLUSIONS
The SHR may be useful to model some aspects (particularly hypertension-related) of memory disorders, especially those in which cholinergic function is altered.
Hernandez
Caterina M
CM
Program in Clinical and Experimental Therapeutics, University of Georgia, College of Pharmacy, Augusta, GA 30912-2450, USA.
Høifødt
Helga
H
Terry
Alvin V
AV
D000375:Aging / Q000502:physiology; D000818:Animals; D001665:Binding Sites; D015415:Biomarkers; D001921:Brain / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D006973:Hypertension / Q000150:complications* / Q000378:metabolism*; D015151:Immunoblotting; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000175:diagnosis* / Q000378:metabolism*; D018727:Muscarinic Antagonists / Q000493:pharmacokinetics; D018722:Nicotinic Agonists / Q000493:pharmacokinetics; D010890:Pirenzepine / Q000493:pharmacokinetics; D011725:Pyridines / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D011950:Receptors, Cholinergic / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism; D017661:Receptors, Presynaptic / Q000378:metabolism
D015415:Biomarkers; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018727:Muscarinic Antagonists; D018722:Nicotinic Agonists; D011725:Pyridines; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D017661:Receptors, Presynaptic; D010890:Pirenzepine; C082748:epibatidine