Biomedical subjects

Nii A Addy

Publications and source records attributed to Nii A Addy.

4 recordsLinked to original sources

PubMed2005

Impaired synaptic plasticity and learning in mice lacking beta-adducin, an actin-regulating protein.

The adducin family of proteins interacts with the actin cytoskeleton and the plasma membrane in a calcium- and cAMP-dependent manner. Thus, adducins may be involved in changes in cytoskeletal organization resulting from synaptic stimulation. beta-Adducin knock-out mice were examined in physiological and behavioral paradigms related to synaptic plasticity to elucidate the role the adducin family plays in processes underlying learning and memory. In situ hybridization for alpha- and beta-adducin demonstrates that these mRNAs are found throughout the brain, with high levels of expression in the hippocampus. Schaffer collateral-CA1 tetanic long-term potentiation decayed rapidly in acute hippocampal slices from beta-adducin knock-out mice, although baseline spine morphology and postsynaptic density were normal. Interestingly, the input-output relationship was significantly increased in hippocampal slices from beta-adducin knock-out mice. Furthermore, beta-adducin knock-out mice were impaired in performance of fear conditioning and the water maze paradigm. The current results indicate that beta-adducin may play an important role in the cellular mechanisms underlying activity-dependent synaptic plasticity associated with learning and memory.

Actins↗

PubMed2005

Reversal of clozapine effects on working memory in rats with fimbria-fornix lesions.

Clozapine is an effective antipsychotic drug, but its effects on cognitive function are unclear. Previously, we found that clozapine caused a working memory deficit, which was reversed by nicotine. Hippocampal systems are important in determining clozapine effect on memory. In the current study, the memory effects of clozapine and nicotine administration were determined in rats with lesions of the fimbria-fornix, a fiber bundle which carries cholinergic and other projections between the septum and the hippocampus. Female Sprague-Dawley rats were trained on a win-shift procedure in the radial-arm maze, in which each arm entry was rewarded once per session. Then, 13 rats received bilateral knife-cut lesions of the fimbria-fornix, while 14 rats underwent sham surgery. The rats were tested after subcutaneous injections with combinations of clozapine (0 and 1.25 mg/kg) and nicotine (0, 0.2, and 0.4 mg/kg). In sham-operated rats, clozapine caused a significant (P<0.005) working memory impairment. Fimbria-fornix lesions also caused a significant (P<0.05) memory impairment. Interestingly, clozapine had the opposite effect on working memory in the lesioned vs sham-operated rats. In contrast to its effects in controls, clozapine (1.25 mg/kg) significantly (P<0.05) attenuated the working memory deficit caused by fimbria-fornix lesions. Nicotine (0.2 mg/kg) did not quite significantly improve memory in lesioned rats. The effects of clozapine and nicotine were not additive in the lesioned rats. This study demonstrates the efficacy of clozapine in improving working memory in fimbria-fornix-lesioned rats, whereas it causes impairments in intact rats. Therapeutic treatment with clozapine in people with malfunctions of the hippocampus such as seen in schizophrenia may improve cognitive performance, whereas the same doses of clozapine may impair memory in individuals without hippocampal malfunction.

Animals↗

PubMed2003

Ventral hippocampal NMDA blockade and nicotinic effects on memory function.

Nicotinic acetylcholine and NMDA glutamate receptors play critical roles in memory function. The brain areas involved in their interaction are still under investigation. One likely area is the hippocampus. Ventral hippocampal administration of nicotinic antagonists impair memory. Hippocampal administration of NMDA antagonists also cause memory impairments. We evaluated the importance of ventral hippocampal NMDA receptors for nicotinic actions on memory by testing the impact of systemic nicotine on memory with and without administration of the NMDA antagonist dizocilpine into the ventral hippocampus. Sprague-Dawley rats (N=11) trained on the 16-arm radial maze were bilaterally implanted with local infusion cannulae in the ventral hippocampus. The effects on memory function of ventral hippocampal infusions of 0, 2, 6 and 18 microg per side of dizocilpine were examined with and without acute systemic nicotine administration (0 or 0.4 mg/kg). The dizocilpine doses tested did not cause memory deficits by themselves but only did so when given in combination with systemic nicotine. Blocking NMDA ventral hippocampal actions revealed an impairing action of nicotine on memory. Nicotine effects on other non-NMDA hippocampal receptor systems or extra-hippocampal systems may have been left unchecked by the diminished nicotinic effect on ventral hippocampal NMDA receptors.

Animals↗

PubMed2003

Nicotinic mechanisms of memory: effects of acute local DHbetaE and MLA infusions in the basolateral amygdala.

Nicotine has been shown to improve working memory. The neural mechanisms underlying this effect are still being determined. The ventral hippocampus is critical for nicotinic effects on memory. Local ventral hippocampal infusions of either the nicotinic alpha7 nicotinic receptor antagonist methyllycaconitine (MLA) or the alpha4beta2 nicotinic receptor antagonist dihydro-beta-erythroidine (DHbetaE) caused working memory impairments, but no additive effects were seen. Other areas, such as the amygdala, also likely play important roles in nicotinic effects on memory. Amygdalar lesions cause memory impairment and there is a dense concentration of nicotinic receptors in the basolateral amygdala. The current study used local basolateral amygdalar infusions of the nicotinic antagonists MLA and DHbetaE to determine the involvement of alpha7 and alpha4beta2 nicotinic receptors in spatial working and reference memory. Rats (n=8) were trained in the 16-arm radial maze and were implanted with bilateral infusion cannulae into the basolateral amygdala. Acute infusions of MLA (6.75 micro g/side, P<0.0005) or DHbetaE (3.38 micro g/side, P<0.025) caused significant working memory impairments. When given together MLA and DHbetaE did not produce an additive effect. In fact, the 6.75 micro g/kg dose of DHbetaE produced a significant (P<0.0005) attenuation of the MLA-induced working memory impairment. Significant effects were not seen with reference memory or response latency. Nicotinic systems in the basolateral amygdala, as in the ventral hippocampus, are important for spatial working memory. In both the basolateral amygdala and the ventral hippocampus, MLA and DHbetaE individually caused working memory impairments. The lowest effective dose of DHbetaE was lower in the basolateral amygdala than in the ventral hippocampus. In both the basolateral amygdala and the ventral hippocampus, combined MLA and DHbetaE treatment did not produce additive working memory deficits. Unlike in the ventral hippocampus, the addition of DHbetaE to MLA in the basolateral amygdala significantly reduced the MLA-induced working memory deficit.

Aconitine↗