Research reportCharacteristics of changes in cholinergic function and impairment of learning and memory-related behavior induced by olfactory bulbectomy
Introduction
It is well known that Alzheimer's disease (AD) patients show marked impairment of the olfactory system [6], [12], [23], [30]. A recent study has shown that olfaction is impaired in an early stage of AD [13]. The olfactory system is particularly rich in acetylcholine and other neurotransmitters and AD patients have been found to have a reduced activity of ChAT in the olfactory tubercle, indicating that cholinergic neurons may be degenerated in the olfactory system. Furthermore, an increased number of senile plaques containing amyloid β-protein (Aβ) and neurofibrillary tangles in the olfactory bulbs (OB) and anterior olfactory nuclei have been demonstrated in patients with AD [8]. These findings suggest that the olfactory system and AD may be relative to each other.
In animals, the olfactory bulbectomy (OBX) causes various abnormal behaviors, such as muricide [5], reduced sexual behavior [14], [15], increased exploratory behavior [24], impaired learning and memory [27], [31] and reduced rapid eye movement (REM) sleep [21], [22].
It is well known that cholinergic neurons in the brain play an important role in memory function. Several groups have reported that OBX induces a transient increase in choline acetyltransferase (ChAT) levels in the olfactory tubercle [4] and reduced binding of muscarinic receptors [7]. However, the cholinergic neuronal functions and the effect of cholinergic drugs on the impairment of learning and memory-related behavior after OBX remain unclear.
In the present study, memory function after OBX was examined in two tasks, namely, step-through passive avoidance task and elevated plus-maze task. We investigated the effects of cholinergic drugs on learning and memory-related behavior and cholinergic neuronal function after OBX.
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Animals
Adult male ddY mice weighing 23–26 g were obtained from Nippon SLC (Hamamatsu, Japan). Animals were housed in cages with free access to food and water under the condition of constant temperature (23±1 °C) and humidity (55±5%) and a 12-h light/dark cycle (09:00–21:00 h). All experiments were performed according to the Guide for Care and Use of Laboratory Animals at Tohoku Pharmaceutical University.
Surgery
Mice anesthetized with pentobarbital Na (50 mg/kg, i.p.; Dainippon, Osaka, Japan) were placed in a
Influence of OBX on learning and memory-related behavior
The latency time was not significantly changed on the 1st day after OBX as compared with the sham mice (U=17.5, P=0.19). However, on days 7 (U=14, P<0.05) and 14 (U=9.0, P<0.01) after OBX, the latency time of the retention trial was gradually significantly decreased as compared to the sham mice (Fig. 1). Using the elevated plus-maze, the transfer latency time of the retention trial on days 7 (U=36, P=0.29) and 14 (U=23, P=0.16) after OBX was not significant compared with the sham mice (Table 1,
Discussion
Memory function after OBX was examined by two different tasks: elevated plus-maze performance and passive-avoidance behavior. In the present study using a passive-avoidance task, the learning and memory-related behavior was impaired on days 7 and 14 after OBX (Fig. 1). This finding is consistent with previously reported results measured by the eight-arm radial maze [9], the Morris water maze [20], the three-panel runway apparatus and the three-lever operant task [31]. However, the escape
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