Synaptic Plasticity Changes: Hallmark for Neurological and Psychiatric Disorders

Abstract

[...]synaptic dysfunction is involved in a great number of neurological conditions, such as neurodegenerative diseases (Alzheimer’s, Parkinson’s, and Huntington’s disease), dystonia, levodopa-induced dyskinesia, and ischemia [1–8], as well as neuropsychiatric conditions such as autism, schizophrenia, and major depression [9–15]. [...]synaptic plasticity alterations can appear in an early asymptomatic phase of the disease [16, 17]. [...]the aim of this special issue is to highlight synaptic plasticity changes as a hallmark of neurological and neuropsychiatric diseases. J. E. Orfila et al. used a model of cardiac arrest and cardiopulmonary resuscitation (CA/CPR) to produce global brain ischemia and assess whether ischemic LTP (a pathological form of synaptic plasticity induced in acute brain slices by oxygen and glucose deprivation) is reproduced in vivo. In this review, the authors summarize recent evidence on the role of hydrogen sulfide, nitric oxide, and carbon monoxide in synaptic plasticity, emphasizing that these gaseous neurotransmitters can play roles in neurological conditions such as schizophrenia, bipolar disorder, major depressive disorder, and Alzheimer’s disease.

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Many molecular mechanisms cooperate to produce synaptic plasticity changes. These include alterations in neurotransmitter release and in the effectiveness of neuronal response to those neurotransmitters. Defining and understanding how these mechanisms are involved in neuropathological conditions are a major challenge for neuroscience in the third millennium.

Indeed, synaptic dysfunction is involved in a great number of neurological conditions, such as neurodegenerative diseases (Alzheimer’s, Parkinson’s, and Huntington’s disease), dystonia, levodopa-induced dyskinesia, and ischemia [1–8], as well as neuropsychiatric conditions such as autism, schizophrenia, and major depression [9–15]. Moreover, synaptic plasticity alterations can appear in an early asymptomatic phase of the disease [16, 17].

Therefore, the aim of this special issue is to highlight synaptic plasticity changes as a hallmark of neurological and neuropsychiatric diseases.

In this issue, M. Cantone et al. report altered mechanisms of neural plasticity associated with long-term hand motor deficits in adult patients with intellectual disability. Intellectual disability is commonly associated with impairments in psychomotor skills and abilities of daily living. These authors studied the effects of a two-month program of hand-motor rehabilitation and visual-perceptual treatment in a population of 30 subjects with mild intellectual impairment. The study reports that this group had significantly better motor performance compared to an intellectually impaired group that received conventional rehabilitation. These results suggest that a program that emphasizes visual-perceptual and motor skills may be superior to conventional rehabilitation in improving motor function in the mildly intellectually impaired individuals. From a neuroanatomical perspective, motor learning requires the development and retention of several skills, depending on the structural and functional integrity of the neostriatum and the cerebellum. These brain structures are considered the substrate of learning and memory, both in development and aging and in physiological and pathological conditions [18]. The findings from this report open new exciting windows on the noninvasive rehabilitative interventions targeting the cortical plasticity and neural connectivity.

C, Terranova et al. investigated the mechanism contributing to the selection of voluntary movements in focal hand dystonia, a syndrome characterized by muscle spasms giving rise to involuntary movements and abnormal postures. Significant alterations in synaptic plasticity were described in dystonic animal models as well as in patients [6, 19–22]. In the present work, the authors evaluated the spatial and temporal somatosensory integration by recording somatosensory evoked potentials (SEPs) in controls and patients with focal dystonia. Patients usually present two main abnormalities: greater facilitation and loss of spatial specificity. Here, the authors demonstrated that the inhibitory integration of somatosensory inputs in focal hand dystonia is normal during sensory-motor plasticity.

J. E. Orfila et al. used a model of cardiac arrest and cardiopulmonary resuscitation (CA/CPR) to produce global brain ischemia and assess whether ischemic LTP (a pathological form of synaptic plasticity induced in acute brain slices by oxygen and glucose deprivation) is reproduced in vivo. Indeed, the authors found an increased postsynaptic glutamate receptor phosphorylation and function and a preserved ability to depotentiate CA1 synapses. Ischemic LTP was found to occlude physiological LTP, providing a possible target for interventional strategies to improve memory function after cardiac arrest. This is the first study to demonstrate that in vivo ischemia causes synaptic alterations that are consistent with ischemic LTP and represent a new model to characterize aberrant forms of synaptic plasticity.

In the last section of this issue, three reviews point to the attention on the molecular mechanisms underlying synaptic plasticity alterations.

U. Shefa et al. discuss the role of diffusible gaseous transmitters (gasotransmitters) in regulating neuronal excitability and plasticity. In this review, the authors summarize recent evidence on the role of hydrogen sulfide, nitric oxide, and carbon monoxide in synaptic plasticity, emphasizing that these gaseous neurotransmitters can play roles in neurological conditions such as schizophrenia, bipolar disorder, major depressive disorder, and Alzheimer’s disease. They suggest that rescuing homeostatic levels of gasotransmitters may restore synaptic plasticity and proper neuronal functioning.

P. Olivero et al. perform a thorough analysis of the role of mitochondria in synaptic alterations underlying psychiatric and neurodegenerative disorders. The efficiency of the cellular physiological processes is governed by an appropriate protein localization and function. A molecular network, called the proteostasis network, participates in the intricate mechanisms of synthesis, folding, trafficking, and degradation necessary to ensure the structure and function of proteins. Dysfunction of the proteostatic network affects neuronal plasticity, and the authors discuss the role of some proteins involved in common diseases, in plasticity alteration and neurodegeneration.

The inflammatory cytokines tumor necrosis factor (TNF) and interleukin-1β (IL-1β) play important physiological roles in LTP and synaptic scaling. However, actions of these cytokines on synaptic plasticity can be altered under conditions of neuroinflammation. F. R. Rizzo et al. provide a timely summary of the important effects of inflammatory cytokines on synaptic plasticity in health and disease and discuss the role of TNF and IL-1β in synaptic plasticity under either physiological or inflammatory conditions, with special emphasis on experimental allergic encephalitis and multiple sclerosis.

The contributions collected in the present issue show the importance of correct synaptic adaptations in the maintenance of a physiological state. Overall, these works show that indeed synaptic plasticity changes may represent a hallmark for neurological and psychiatric disorders.

Conflicts of Interest

All the authors declare that no competing financial interests exist.

Giuseppina Martella Paola Bonsi Steven W. Johnson Angelo Quartarone

References

[1] A. Quartarone, J. Classen, F. Morgante, K. Rosenkranz, M. Hallett, "Consensus paper: use of transcranial magnetic stimulation to probe motor cortex plasticity in dystonia and levodopa-induced dyskinesia," Brain Stimulation, vol. 2 no. 2, pp. 108-117, DOI: 10.1016/j.brs.2008.09.010, 2009.

[2] L. A. Raymond, "Striatal synaptic dysfunction and altered calcium regulation in Huntington disease," Biochemical and Biophysical Research Communications, vol. 483 no. 4, pp. 1051-1062, DOI: 10.1016/j.bbrc.2016.07.058, 2017.

[3] P. Calabresi, A. Pisani, J. Rothwell, V. Ghiglieri, J. A. Obeso, B. Picconi, "Hyperkinetic disorders and loss of synaptic downscaling," Nature Neuroscience, vol. 19 no. 7, pp. 868-875, DOI: 10.1038/nn.4306, 2016.

[4] T. Schirinzi, G. Madeo, G. Martella, M. Maltese, B. Picconi, P. Calabresi, A. Pisani, "Early synaptic dysfunction in Parkinson’s disease: insights from animal models," Movement Disorders, vol. 31 no. 6, pp. 802-813, DOI: 10.1002/mds.26620, 2016.

[5] A. Stefani, E. Olivola, M. Bassi, V. Pisani, P. Imbriani, A. Pisani, M. Pierantozzi, "Strength and weaknesses of cerebrospinal fluid biomarkers in Alzheimer’s disease and possible detection of overlaps with frailty process," CNS & Neurological Disorders Drug Targets, vol. 12 no. 4, pp. 538-546, DOI: 10.2174/1871527311312040016, 2013.

[6] G. Martella, A. Tassone, G. Sciamanna, P. Platania, D. Cuomo, M. T. Viscomi, P. Bonsi, E. Cacci, S. Biagioni, A. Usiello, G. Bernardi, N. Sharma, D. G. Standaert, A. Pisani, "Impairment of bidirectional synaptic plasticity in the striatum of a mouse model of DYT1 dystonia: role of endogenous acetylcholine," Brain, vol. 132 no. 9, pp. 2336-2349, DOI: 10.1093/brain/awp194, 2009.

[7] P. Calabresi, E. Saulle, D. Centonze, A. Pisani, G. A. Marfia, G. Bernardi, "Post-ischaemic long-term synaptic potentiation in the striatum: a putative mechanism for cell type-specific vulnerability," Brain, vol. 125 no. 4, pp. 844-860, DOI: 10.1093/brain/awf073, 2002.

[8] P. Calabresi, D. Centonze, A. Pisani, L. M. Cupini, G. Bernardi, "Synaptic plasticity in the ischaemic brain," Lancet Neurology, vol. 2 no. 10, pp. 622-629, DOI: 10.1016/S1474-4422(03)00532-5, 2003.

[9] C. Hansel, "Deregulation of synaptic plasticity in autism," Neuroscience Letters,DOI: 10.1016/j.neulet.2018.02.003, 2018.

[10] E. Nanou, W. A. Catterall, "Calcium channels, synaptic plasticity, and neuropsychiatric disease," Neuron, vol. 98 no. 3, pp. 466-481, DOI: 10.1016/j.neuron.2018.03.017, 2018.

[11] Y. Sattar, J. Wilson, A. M. Khan, M. Adnan, D. Azzopardi Larios, S. Shrestha, Q. Rahman, Z. Mansuri, A. Hassan, N. B. Patel, N. Tariq, S. Latchana, S. C. Lopez Pantoja, S. Vargas, N. A. Shaikh, F. Syed, D. Mittal, F. Rumesa, "A review of the mechanism of antagonism of N-methyl-D-aspartate receptor by ketamine in treatment-resistant depression," Cureus, vol. 10 no. 5, article e2652,DOI: 10.7759/cureus.2652, 2018.

[12] G. Martella, M. Meringolo, L. Trobiani, A. De Jaco, A. Pisani, P. Bonsi, "The neurobiological bases of autism spectrum disorders: the R451C-neuroligin 3 mutation hampers the expression of long-term synaptic depression in the dorsal striatum," The European Journal of Neuroscience, vol. 47 no. 6, pp. 701-708, DOI: 10.1111/ejn.13705, 2018.

[13] F. E. Henry, W. Hockeimer, A. Chen, S. P. Mysore, M. A. Sutton, "Mechanistic target of rapamycin is necessary for changes in dendritic spine morphology associated with long-term potentiation," Molecular Brain, vol. 10 no. 1,DOI: 10.1186/s13041-017-0330-y, 2017.

[14] E. Santini, T. N. Huynh, A. F. MacAskill, A. G. Carter, P. Pierre, D. Ruggero, H. Kaphzan, E. Klann, "Exaggerated translation causes synaptic and behavioural aberrations associated with autism," Nature, vol. 493 no. 7432, pp. 411-415, DOI: 10.1038/nature11782, 2013.

[15] N. H. Jung, W. G. Janzarik, I. Delvendahl, A. Münchau, M. Biscaldi, F. Mainberger, T. Bäumer, R. Rauh, V. Mall, "Impaired induction of long-term potentiation-like plasticity in patients with high-functioning autism and Asperger syndrome," Developmental Medicine and Child Neurology, vol. 55 no. 1, pp. 83-89, DOI: 10.1111/dmcn.12012, 2013.

[16] G. Madeo, T. Schirinzi, G. Martella, E. C. Latagliata, F. Puglisi, J. Shen, E. M. Valente, M. Federici, N. B. Mercuri, S. Puglisi-Allegra, P. Bonsi, A. Pisani, "PINK1 heterozygous mutations induce subtle alterations in dopamine-dependent synaptic plasticity," Movement Disorders, vol. 29 no. 1, pp. 41-53, DOI: 10.1002/mds.25724, 2014.

[17] E.-K. Tan, F. S. Refai, M. Siddique, K. Yap, P. Ho, S. Fook-Chong, Y. Zhao, "Clinically reported heterozygous mutations in the PINK1 kinase domain exert a gene dosage effect," Human Mutation, vol. 30 no. 11, pp. 1551-1557, DOI: 10.1002/humu.21108, 2009.

[18] J. D. Sweatt, "The emerging field of neuroepigenetics," Neuron, vol. 80 no. 3, pp. 624-632, DOI: 10.1016/j.neuron.2013.10.023, 2013.

[19] M. Maltese, J. Stanic, A. Tassone, G. Sciamanna, G. Ponterio, V. Vanni, G. Martella, P. Imbriani, P. Bonsi, N. B. Mercuri, F. Gardoni, A. Pisani, "Early structural and functional plasticity alterations in a susceptibility period of DYT1 dystonia mouse striatum," eLife, vol. 7,DOI: 10.7554/eLife.33331, 2018.

[20] G. Martella, M. Maltese, R. Nisticò, T. Schirinzi, G. Madeo, G. Sciamanna, G. Ponterio, A. Tassone, G. Mandolesi, V. Vanni, M. Pignatelli, P. Bonsi, A. Pisani, "Regional specificity of synaptic plasticity deficits in a knock-in mouse model of DYT1 dystonia," Neurobiology of Disease, vol. 65, pp. 124-132, DOI: 10.1016/j.nbd.2014.01.016, 2014.

[21] A. Quartarone, A. Pisani, "Abnormal plasticity in dystonia: disruption of synaptic homeostasis," Neurobiology of Disease, vol. 42 no. 2, pp. 162-170, DOI: 10.1016/j.nbd.2010.12.011, 2011.

[22] A. Quartarone, V. Rizzo, C. Terranova, F. Morgante, S. Schneider, N. Ibrahim, P. Girlanda, K. P. Bhatia, J. C. Rothwell, "Abnormal sensorimotor plasticity in organic but not in psychogenic dystonia," Brain, vol. 132 no. 10, pp. 2871-2877, DOI: 10.1093/brain/awp213, 2009.