Spontaneously hypertensive rats: Further evaluation of age-related memory performance and cholinergic marker expression

Caterina M. Hernandez, Helga Høifødt, Alvin V Terry

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

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. Method: 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 α3 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. MI 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 α3-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. Conclusion: The SHR may be useful to model some aspects (particularly hypertension-related) of memory disorders, especially those in which cholinergic function is altered.

Original languageEnglish (US)
Pages (from-to)197-209
Number of pages13
JournalJournal of Psychiatry and Neuroscience
Volume28
Issue number3
StatePublished - May 1 2003

Fingerprint

Inbred SHR Rats
Cholinergic Agents
Vesicular Acetylcholine Transport Proteins
epibatidine
Memory Disorders
Nicotinic Receptors
Phenotype
Choline O-Acetyltransferase
Inbred WKY Rats
Superior Colliculi
Putamen
Task Performance and Analysis
Cholinergic Receptors
Autoradiography
Short-Term Memory
Immunoblotting
Rodentia
Hippocampus
Cardiovascular Diseases
Central Nervous System

Keywords

  • Acetylcholine
  • Aging
  • Animal
  • Cholinergic
  • Hypertension
  • Memory disorders
  • Models
  • Rats, inbred SHR
  • Rats, inbred WKY
  • Receptors

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)

Cite this

Spontaneously hypertensive rats : Further evaluation of age-related memory performance and cholinergic marker expression. / Hernandez, Caterina M.; Høifødt, Helga; Terry, Alvin V.

In: Journal of Psychiatry and Neuroscience, Vol. 28, No. 3, 01.05.2003, p. 197-209.

Research output: Contribution to journalArticle

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N2 - 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. Method: 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 α3 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. MI 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 α3-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. Conclusion: The SHR may be useful to model some aspects (particularly hypertension-related) of memory disorders, especially those in which cholinergic function is altered.

AB - 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. Method: 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 α3 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. MI 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 α3-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. Conclusion: The SHR may be useful to model some aspects (particularly hypertension-related) of memory disorders, especially those in which cholinergic function is altered.

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