Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.
Eur J Pharmacol. 2010 Jan 10;626(1):9-17. doi: 10.1016/j.ejphar.2009.09.070. Epub 2009 Oct 18.
Neuropeptides represent by far the most common signalling molecules in the central nervous system. They are involved in a wide range of physiological functions and can act as neurotransmitters, neuromodulators or hormones in the central nervous system and in the periphery. Accumulating evidence during the past 40 years has implicated a number of neuropeptides in various cognitive functions including learning and memory. A major focus has been on the possibility that neuropeptides, by coexisting with classical neurotransmitters, can modulate classical transmitter function of importance for cognition. It has become increasingly clear that most transmitter systems in the brain can release a cocktail of signalling molecules including classical transmitters and several neuropeptides. However, the neuropeptides seem to come into action mainly under conditions of severe stress or aversive events, which have linked their action also to regulation of affective components of behaviour. This paper summarises some of the results of three neuropeptides, which can impact on hippocampal cognition by intrinsic (dynorphins, nociceptin) or extrinsic (galanin) modulation. The results obtained with these neuropeptides in rodent studies indicate that they are important for various aspects of hippocampal learning and memory as well as hippocampal plasticity. Recent studies in humans have also shown that dysregulation of these neuropeptides may be of importance for both neurodegenerative and neuropsychiatric disorders associated with cognitive impairments. It is concluded that compounds acting on neuropeptide receptor subtypes will represent novel targets for a number of disorders, which involve cognitive deficiencies.
神经肽是迄今为止中枢神经系统中最常见的信号分子。它们参与广泛的生理功能,可以作为神经递质、神经调质或激素在中枢神经系统和外周发挥作用。在过去的 40 年中,越来越多的证据表明,一些神经肽参与了各种认知功能,包括学习和记忆。一个主要的焦点是,神经肽通过与经典神经递质共存,可以调节对认知很重要的经典递质功能。越来越明显的是,大脑中的大多数递质系统都可以释放包括经典递质和几种神经肽在内的信号分子混合物。然而,神经肽似乎主要在严重应激或厌恶事件的情况下发挥作用,这也将它们的作用与行为的情感成分的调节联系起来。本文总结了三种神经肽的一些结果,它们可以通过内在(强啡肽、孤啡肽)或外在(甘丙肽)调节对海马认知产生影响。这些神经肽在啮齿动物研究中的结果表明,它们对海马学习和记忆以及海马可塑性的各个方面都很重要。最近在人类中的研究也表明,这些神经肽的失调可能对与认知障碍相关的神经退行性和神经精神疾病都很重要。结论是,作用于神经肽受体亚型的化合物将成为涉及认知缺陷的许多疾病的新靶点。