Adrenergic receptor β3 is involved in the memory consolidation process in mice

Abstract

Attention and emotion have a positive impact on memory formation, which is related to the activation of the noradrenergic system in the brain. The hippocampus and amygdala are fundamental structures in memory acquisition, which is modulated by noradrenaline through the noradrenergic receptors. Pharmacological studies suggest that memory acquisition depends on the action of both the β3 (β3-AR) and β2 (β2-AR) receptor subtypes. However, the use of animal models with specific knockout for the β3-AR receptor only (β3-ARKO) allows researchers to more accurately assess its role in memory formation processes. In the present study, we evaluated short- and long-term memory acquisition capacity in β3-ARKO mice and wild-type mice at approximately 60 days of age. The animals were submitted to the open field test, the elevated plus maze, object recognition, and social preference. The results showed that the absence of the β3-AR receptor caused no impairment in locomotion and did not cause anxious behavior, but it caused significant impairment of short- and long-term memory compared to wild-type animals. We also evaluated the expression of genes involved in memory consolidation. The mRNA levels for GLUT3, a glucose transporter expressed in the central nervous system, were significantly reduced in the amygdala, but not in the hippocampus of the β3-ARKO animals. Our results showed that β3-AR was involved in the process of acquisition of declarative memory, and its action may be due to the facilitation of glucose absorption in the amygdala.

Environmental enrichment reverses memory impairment in B3-ARKO mice

“…WT mice spent significantly more time with the new object, 3h (O2) (p<0.0001; t=5.06) and 24 h (O3) (p<0.0001; t=8.52) after the familiarization period(Figures 3 A-B). In contrast, the Adrβ3KO spent similar amounts of time with old (O1) and new objects (O2) 3 h (p=0.62; t=1.03) and 24h (O3) (p=0.1; t=2.06) after the familiarization period(Figure 3 A-B), confirming data from a previous study(13) showing that the absence of Adrβ3 impairs memory consolidation. Remarkably, EE was effective in correcting the memory impairment displayed by the Adrβ3KO mice both 3h (O2) (p<0.0001; t=8.06) and 24 h (O3) (p=0.0014; t=3.73) after the familiarization period(Figure 3 C-D).…”

“…Isopropoterenol, an agonist for Adrβ1 and Adrβ2, increases neural plasticity in the CA1 and CA3 regions and in the dentate gyrus in the hippocampus, while propranolol, a Adrβ1 and Adrβ2 antagonist, blocks LTP in the CA1 region and the dentate gyrus (9)(10)(11)(12). In addition, the absence of the Adrβ3 receptor induces important deficits in the formation of short-and long-term memory (13).…”

Everything You Always Wanted to Know about β3-AR * (* But Were Afraid to Ask)

“…Gibbs et al showed that memory formation at the time of learning is enhanced by the administration of β 3 -AR agonist CL316243 to day-old chicks, a process most likely due to an increase in glucose uptake via GLUT3 [163]. Interestingly, β 3 -AR KO mice show a decrease in mRNA level of GLUT3 transporter in the amygdala and impairments in long- and short-term memory formation [164].…”

Multisensory Stimulation Reverses Memory Impairment in Adrβ3KO Mice

“…This also drives neuronal activity in the locus coeruleus (the main point from which 2 noradrenergic neurons project throughout the brain), and is partially blocked by inhibition of Adrβs [7,8]. Although the role of Adrβ1 and Adrβ2 is well established, a recent increase in experimental evidence has been bringing light to the role of Adrβ 3 as a key role in mediate memory consolidation in rodents [9,10]. Confirming its relevance, the administration of Adrβ3 agonist reversed the memory impairment of animal models for Alzheimer's disease [11].…”

“…Deletion of astrocytic EAAT2, the major glutamate transporter in the brain, leads to early deficits in short-term memory and in spatial reference learning and longterm memory [18]. Considering that the inactivation of Adrβ3 induces a significant impairment in short-and long-term memory [10] and that the neuroinflammation controls it [19], we hypothesized that the use of MS could reverse the memory impairment exhibited by the Adrβ3 knock-out (Adrβ3KO) mice. The cognitive impairment exhibited by Adrβ3KO mice at 120 days of life was rescued when an 8-week program of MS was initiated after weaning at 21 days of life.…”