Targeting the gastrin-releasing peptide receptor pathway to treat cognitive dysfunction associated with Alzheimer's Disease

Roesler, Rafaël; Luft, Tatiana; Schwartsmann, Gilberto

doi:10.1590/s1980-57642008dn10200002

Cited by 3 publications

(3 citation statements)

References 44 publications

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“…When DHA reaches the lumen of the GI tract and/or the hippocampus, it is likely to induce GRP–GRPR activity and hence might affect GI tract and hippocampus functions. GRP and GRPR binding might activate PKC or PKA and affect their downstream signaling [ 45 ] in neurons.…”

Section: Discussionmentioning

confidence: 99%

Docosahexaenoic Acid Helps to Lessen Extinction Memory in Rats

et al. 2018

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Memory extinction is referred to as a learning process in which a conditioned response (CR) progressively reduces over time as an animal learns to uncouple a response from a stimulus. Extinction occurs when the rat is placed into a context without shock after training. Docosahexaenoic acid (DHA, C22:6, n-3) is implicated in memory formation in mammalian brains. In a two-way active shuttle-avoidance apparatus, we examined whether DHA affects the extinction memory and the expression of brain cognition-related proteins, including gastrin-releasing peptide receptor (GRPR), brain-derived neurotrophic factor receptor (BDNFR) tyrosine kinase receptor B (TrKB), and N-methyl-d-aspartate receptor (NMDAR) subunits NR2A and NR2B. Also, the protein levels of GRP, BDNF, postsynaptic density protein-95 (PSD-95), and vesicular acetylcholine transporter (VAChT), and the antioxidative potentials, in terms of lipid peroxide (LPO) and reactive oxygen species (ROS), were examined in the hippocampus. During the acquisition phase, the rats received a conditioned stimulus (CS-tone) paired with an unconditioned stimulus (UCS foot shock) for three consecutive days (Sessions S1, S2, and S3, each consisting of 30-trials) after 12 weeks of oral administration of DHA. After a three-day interval, the rats were re-subjected to two extinction sessions (S4, S5), each comprising 30 trials of CS alone. During the acquisition training in S1, the shock-related avoidance frequency (acquisition memory) was significantly higher in the DHA-administered rats compared with the control rats. The avoidance frequency, however, decreased with successive acquisition trainings in sessions S2 and S3. When the rats were subjected to the extinction sessions after a break for consolidation, the conditioned response (CR) was also significantly higher in the DHA-administered rats. Interestingly, the freezing responses (frequency and time) also significantly decreased in the DHA-administered rats, thus suggesting that a higher coping capacity was present during fear stress in the DHA-administered rats. DHA treatments increased the mRNA levels of GRPR, BDNF receptor TrKB, and NMDAR subunit NR2B. DHA also increased the protein levels of GRP, BDNF, PSD-95, and VAChT, and the antioxidative potentials in the hippocampus. These results suggest the usefulness of DHA for treating stress disorders.

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Section: Discussionmentioning

confidence: 99%

Docosahexaenoic Acid Helps to Lessen Extinction Memory in Rats

et al. 2018

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“…Since the bombesin receptor subtype 3, the mammalian ortholog of CCHa2-R, is also implicated in memory consolidation ( Flood and Morley, 1988 ; Shumyatsky et al, 2002 ; Roesler et al, 2004 ; Ghanbari et al, 2018 ; Melzer et al, 2021 ), our findings may further reinforce the evolutionarily conserved function of the CCHa2 system. Moreover, it is noteworthy that the bombesin receptor is involved in the etiology of Alzheimer’s disease ( Roesler et al, 2007 ). The notion is supported by the abnormal receptor signaling observed in the patient’s fibroblasts and a transgenic mouse model of Alzheimer’s disease ( Ito et al, 1994 ; Huang et al, 2005 ).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, decades of research critically conjoined the bombesin receptor function in memory consolidation ( Flood and Morley, 1988 ; Shumyatsky et al, 2002 ; Roesler et al, 2004 ; Ghanbari et al, 2018 ; Melzer et al, 2021 ). Abnormalities in the bombesin receptor pathway in patients with Alzheimer’s disease ( Roesler et al, 2007 ) suggest an as-yet-unsolved cognitive feature of the metabolic neuropeptide family. However, any attributes that signify CCHa2’s function in the cognitive process are so far unclear.…”

Section: Introductionmentioning

confidence: 99%

Nutrient responding peptide hormone CCHamide-2 consolidates appetitive memory

Yamagata

Imanishi²,

Wu³

et al. 2022

Front. Behav. Neurosci.

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CCHamide-2 (CCHa2) is a protostome excitatory peptide ortholog known for various arthropod species. In fruit flies, CCHa2 plays a crucial role in the endocrine system, allowing peripheral tissue to communicate with the central nervous system to ensure proper development and the maintenance of energy homeostasis. Since the formation of odor-sugar associative long-term memory (LTM) depends on the nutrient status in an animal, CCHa2 may play an essential role in linking memory and metabolic systems. Here we show that CCHa2 signals are important for consolidating appetitive memory by acting on the rewarding dopamine neurons. Genetic disruption of CCHa2 using mutant strains abolished appetitive LTM but not short-term memory (STM). A post-learning thermal suppression of CCHa2 expressing cells impaired LTM. In contrast, a post-learning thermal activation of CCHa2 cells stabilized STM induced by non-nutritious sugar into LTM. The receptor of CCHa2, CCHa2-R, was expressed in a subset of dopamine neurons that mediate reward for LTM. In accordance, the receptor expression in these dopamine neurons was required for LTM specifically. We thus concluded that CCHa2 conveys a sugar nutrient signal to the dopamine neurons for memory consolidation. Our finding establishes a direct interplay between brain reward and the putative endocrine system for long-term energy homeostasis.

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Can dipeptidyl peptidase-4 inhibitors treat cognitive disorders?

Cheng

Cordato

et al. 2020

Pharmacology & Therapeutics

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Targeting the gastrin-releasing peptide receptor pathway to treat cognitive dysfunction associated with Alzheimer's Disease

Cited by 3 publications

References 44 publications

Docosahexaenoic Acid Helps to Lessen Extinction Memory in Rats

Docosahexaenoic Acid Helps to Lessen Extinction Memory in Rats

Nutrient responding peptide hormone CCHamide-2 consolidates appetitive memory

Can dipeptidyl peptidase-4 inhibitors treat cognitive disorders?

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